Integrin αvβ6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis
Integrin αvβ6 is rapidly up‐regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibiti...
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| Vydáno v: | Hepatology (Baltimore, Md.) Ročník 63; číslo 1; s. 217 - 232 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.01.2016
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| ISSN: | 0270-9139, 1527-3350 |
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| Abstract | Integrin αvβ6 is rapidly up‐regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6‐dependent TGFβ1 activation. Freshly isolated αvβ6+ liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro, whereas colony formation by epithelial cell adhesion molecule‐positive progenitor cells is blocked by αvβ6‐neutralizing antibody and in integrin beta 6‐deficient cells. Inhibition of progenitors by anti‐αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction. Conclusion: These results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers. (Hepatology 2016;63:217–232) |
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| AbstractList | Integrin αvβ6 is rapidly up-regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6-dependent TGFβ1 activation. Freshly isolated αvβ6(+) liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro, whereas colony formation by epithelial cell adhesion molecule-positive progenitor cells is blocked by αvβ6-neutralizing antibody and in integrin beta 6-deficient cells. Inhibition of progenitors by anti-αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction.
These results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers. Integrin αvβ6 is rapidly up-regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6-dependent TGFβ1 activation. Freshly isolated αvβ6+ liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro, whereas colony formation by epithelial cell adhesion molecule-positive progenitor cells is blocked by αvβ6-neutralizing antibody and in integrin beta 6-deficient cells. Inhibition of progenitors by anti-αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction. UNLABELLEDIntegrin αvβ6 is rapidly up-regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6-dependent TGFβ1 activation. Freshly isolated αvβ6(+) liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro, whereas colony formation by epithelial cell adhesion molecule-positive progenitor cells is blocked by αvβ6-neutralizing antibody and in integrin beta 6-deficient cells. Inhibition of progenitors by anti-αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction.CONCLUSIONThese results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers. Integrin αvβ6 is rapidly up‐regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6‐dependent TGFβ1 activation. Freshly isolated αvβ6+ liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro, whereas colony formation by epithelial cell adhesion molecule‐positive progenitor cells is blocked by αvβ6‐neutralizing antibody and in integrin beta 6‐deficient cells. Inhibition of progenitors by anti‐αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction. Conclusion: These results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers. (Hepatology 2016;63:217–232) Integrin αvβ6 is rapidly up‐regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6‐dependent TGFβ1 activation. Freshly isolated αvβ6 + liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro , whereas colony formation by epithelial cell adhesion molecule‐positive progenitor cells is blocked by αvβ6‐neutralizing antibody and in integrin beta 6‐deficient cells. Inhibition of progenitors by anti‐αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction. Conclusion: These results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers. (H epatology 2016;63:217–232) |
| Author | Peng, Zhen‐Wei Weinreb, Paul H. Sheppard, Dean Dixit, Richa Schuppan, Detlef Ikenaga, Naoki Sverdlov, Deanna Y. Popov, Yury Liu, Susan B. Violette, Shelia Vaid, Kahini A. |
| AuthorAffiliation | 1 Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 2 Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 5 Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, Mainz, Germany 3 Biogen, Inc., Cambridge, MA 4 Lung Biology Center, University of California, San Francisco School of Medicine, San Francisco, CA |
| AuthorAffiliation_xml | – name: 5 Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, Mainz, Germany – name: 3 Biogen, Inc., Cambridge, MA – name: 2 Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA – name: 1 Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China – name: 4 Lung Biology Center, University of California, San Francisco School of Medicine, San Francisco, CA |
| Author_xml | – sequence: 1 givenname: Zhen‐Wei surname: Peng fullname: Peng, Zhen‐Wei organization: Harvard Medical School – sequence: 2 givenname: Naoki surname: Ikenaga fullname: Ikenaga, Naoki organization: Harvard Medical School – sequence: 3 givenname: Susan B. surname: Liu fullname: Liu, Susan B. organization: Harvard Medical School – sequence: 4 givenname: Deanna Y. surname: Sverdlov fullname: Sverdlov, Deanna Y. organization: Harvard Medical School – sequence: 5 givenname: Kahini A. surname: Vaid fullname: Vaid, Kahini A. organization: Harvard Medical School – sequence: 6 givenname: Richa surname: Dixit fullname: Dixit, Richa organization: Harvard Medical School – sequence: 7 givenname: Paul H. surname: Weinreb fullname: Weinreb, Paul H. organization: Biogen, Inc – sequence: 8 givenname: Shelia surname: Violette fullname: Violette, Shelia organization: Biogen, Inc – sequence: 9 givenname: Dean surname: Sheppard fullname: Sheppard, Dean organization: University of California, San Francisco School of Medicine – sequence: 10 givenname: Detlef surname: Schuppan fullname: Schuppan, Detlef organization: University Medical Center – sequence: 11 givenname: Yury surname: Popov fullname: Popov, Yury organization: Harvard Medical School |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26448099$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1038/nature11826 10.1038/nm1377 10.1016/j.ccr.2009.08.021 10.1002/hep.21466 10.1172/JCI23486 10.1053/gast.1996.v111.pm8698195 10.1053/j.gastro.2011.01.040 10.1055/s-2004-815564 10.1053/j.gastro.2008.04.009 10.1002/hep.21849 10.1111/j.1365-2559.2006.02468.x 10.1016/S0140-6736(05)67530-7 10.2353/ajpath.2007.061133 10.1016/j.ajpath.2014.02.020 10.1101/gad.2029411 10.1074/jbc.M312103200 10.1016/j.jhep.2005.06.025 10.1038/nature10152 10.1111/j.1365-2559.2004.01919.x 10.1016/j.ajpath.2013.03.018 10.1002/hep.27659 10.1038/nrgastro.2012.23 10.1002/hep.26753 10.1126/science.1118389 10.1016/j.ajpath.2014.10.013 10.1002/hep.20650 10.1016/S0092-8674(00)80545-0 10.1016/j.jhep.2007.11.021 10.1016/j.stem.2014.06.003 10.1016/j.ccr.2008.03.007 10.1038/nbt.2464 10.1074/jbc.271.42.25976 10.1016/j.stem.2014.09.008 10.1002/hep.23123 10.1016/j.jhep.2005.06.015 10.1016/j.jhep.2009.12.006 10.1002/hep.27425 10.1053/j.gastro.2007.05.012 10.1002/hep.22238 10.1177/41.10.8245410 10.1053/j.gastro.2004.08.006 10.1038/nature01413 10.1101/gad.2027811 10.1083/jcb.133.4.921 10.1053/j.gastro.2014.08.038 10.1242/dev.031369 |
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| Notes | Potential conflict of interest: Dr. Sheppard consults and owns stock in Pliant Therapeutics. He holds intellectual property rights and received grants from Biogen. He advises Genentech. Dr. Schuppan consults and received grants from Boehringer‐Ingelheim. He consults for MSD, Mitsubishi‐Tanabe, and Takeda. Dr. Popov received grants from Biogen and Stromedix. Dr. Violette is employed by and owns stock in Biogen. Dr. Weinreb is employed by and owns stock in Biogen. Supported by research grants from Biogen, Inc., and Stomedix, Inc.; an institutional grant from Department of Medicine, Beth Israel Deaconess Medical Center (to Y.P.); a career development award from The First Affiliated Hospital of Sun Yat‐sen University (to Z.‐W.P.); and grants from the National Natural Science Foundation of China (81301842) and the Pearl River S&T Nova Program (2014J2200087). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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| PublicationTitleAlternate | Hepatology |
| PublicationYear | 2016 |
| References | 2015; 185 2004; 127 2006; 12 2005; 310 2005; 115 2004; 45 1993; 41 2005; 41 2005; 43 2008; 13 2013; 183 2009; 136 2011; 474 1998; 15 2009; 51 2004; 279 2009; 50 2005; 366 2015; 61 2007; 171 2006; 44 2006; 49 2007; 133 1995; 108 2013; 31 2008; 47 2008; 48 2014; 15 2014; 59 1996; 271 1996; 133 1996; 111 1999; 96 2014; 184 2008; 135 2011; 25 2013; 494 2003; 422 2011; 140 2007; 45 2009; 16 2010; 52 2007; 46 2014; 147 2003; 100 2012; 9 2003; 23 (hep28274-bib-0039-20241017) 2006; 49 (hep28274-bib-0029-20241017) 2011; 25 (hep28274-bib-0036-20241017) 2012; 9 (hep28274-bib-0020-20241017) 2005; 43 (hep28274-bib-0018-20241017) 2004; 45 (hep28274-bib-0023-20241017) 1996; 133 (hep28274-bib-0006-20241017) 2008; 47 (hep28274-bib-0033-20241017) 2009; 136 (hep28274-bib-0002-20241017) 2005; 366 (hep28274-bib-0045-20241017) 2005; 310 (hep28274-bib-0031-20241017) 2013; 183 (hep28274-bib-0041-20241017) 2005; 41 (hep28274-bib-0013-20241017) 1999; 96 (hep28274-bib-0010-20241017) 1995; 108 (hep28274-bib-0050-20241017) 2006; 44 (hep28274-bib-0047-20241017) 2015; 61 (hep28274-bib-0024-20241017) 2003; 422 (hep28274-bib-0043-20241017) 1996; 271 (hep28274-bib-0011-20241017) 1993; 41 (hep28274-bib-0038-20241017) 2003; 100 (hep28274-bib-0028-20241017) 2008; 13 (hep28274-bib-0040-20241017) 2003; 23 (hep28274-bib-0044-20241017) 2007; 45 (hep28274-bib-0016-20241017) 2008; 135 (hep28274-bib-0025-20241017) 1996; 111 (hep28274-bib-0009-20241017) 2009; 16 (hep28274-bib-0005-20241017) 2009; 50 (hep28274-bib-0026-20241017) 2004; 279 (hep28274-bib-0008-20241017) 2005; 115 (hep28274-bib-0001-20241017) 2009; 51 (hep28274-bib-0042-20241017) 2007; 133 (hep28274-bib-0032-20241017) 2015; 185 (hep28274-bib-0030-20241017) 2011; 140 (hep28274-bib-0003-20241017) 1998; 15 (hep28274-bib-0046-20241017) 2014; 184 (hep28274-bib-0014-20241017) 2008; 48 (hep28274-bib-0017-20241017) 2007; 46 (hep28274-bib-0019-20241017) 2015; 61 (hep28274-bib-0027-20241017) 2014; 147 (hep28274-bib-0007-20241017) 2006; 12 (hep28274-bib-0037-20241017) 2014; 59 (hep28274-bib-0012-20241017) 2011; 474 (hep28274-bib-0034-20241017) 2014; 15 (hep28274-bib-0035-20241017) 2014; 15 (hep28274-bib-0049-20241017) 2013; 494 (hep28274-bib-0015-20241017) 2010; 52 (hep28274-bib-0021-20241017) 2007; 171 (hep28274-bib-0004-20241017) 2004; 127 (hep28274-bib-0048-20241017) 2011; 25 (hep28274-bib-0022-20241017) 2013; 31 12902545 - Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11881-8 23680654 - Am J Pathol. 2013 Jul;183(1):182-94 19711424 - Hepatology. 2009 Oct;50(4):1294-306 17187411 - Hepatology. 2007 Jan;45(1):31-41 21632826 - Genes Dev. 2011 Jun 1;25(11):1193-203 25503476 - Hepatology. 2015 Jun;61(6):2100-3 22371217 - Nat Rev Gastroenterol Hepatol. 2012 Feb 28;9(4):231-40 18393293 - Hepatology. 2008 May;47(5):1544-56 17600122 - Am J Pathol. 2007 Aug;171(2):525-36 18455123 - Cancer Cell. 2008 May;13(5):394-406 19800575 - Cancer Cell. 2009 Oct 6;16(4):295-308 25312494 - Cell Stem Cell. 2014 Nov 6;15(5):605-18 15521023 - Gastroenterology. 2004 Nov;127(5):1565-77 16532004 - Nat Med. 2006 Apr;12(4):410-6 20137822 - J Hepatol. 2010 Mar;52(3):362-9 17631134 - Gastroenterology. 2007 Jul;133(1):80-90 16210527 - Science. 2005 Oct 7;310(5745):68-71 21632825 - Genes Dev. 2011 Jun 1;25(11):1185-92 8824234 - J Biol Chem. 1996 Oct 18;271(42):25976-80 25478810 - Am J Pathol. 2015 Feb;185(2):325-34 20101749 - Hepatology. 2010 Feb;51(2):660-78 16110324 - J Clin Invest. 2005 Sep;115(9):2330-40 16223543 - J Hepatol. 2005 Dec;43(6):1045-54 23242163 - Nat Biotechnol. 2013 Jan;31(1):63-70 14960589 - J Biol Chem. 2004 Apr 23;279(17 ):17875-87 24115180 - Hepatology. 2014 Apr;59(4):1617-26 16168515 - J Hepatol. 2006 Jan;44(1):167-75 8666675 - J Cell Biol. 1996 May;133(4):921-8 9845427 - Semin Diagn Pathol. 1998 Nov;15(4):259-69 10025398 - Cell. 1999 Feb 5;96(3):319-28 15330800 - Histopathology. 2004 Sep;45(3):226-36 19429791 - Development. 2009 Jun;136(11):1951-60 15793848 - Hepatology. 2005 Apr;41(4):809-18 18538673 - Gastroenterology. 2008 Aug;135(2):660-70 25130492 - Cell Stem Cell. 2014 Sep 4;15(3):340-9 17924447 - Hepatology. 2007 Nov;46(5):1404-12 25203810 - Hepatology. 2015 Feb;61(2):678-91 24681248 - Am J Pathol. 2014 May;184(5):1263-7 25173753 - Gastroenterology. 2014 Dec;147(6):1378-92 8245410 - J Histochem Cytochem. 1993 Oct;41(10):1521-7 14722815 - Semin Liver Dis. 2003 Nov;23(4):385-96 18221819 - J Hepatol. 2008 Mar;48(3):453-64 21677751 - Nature. 2011 Jun 15;474(7351):343-9 12634787 - Nature. 2003 Mar 13;422(6928):169-73 21277850 - Gastroenterology. 2011 May;140(5):1642-52 23354049 - Nature. 2013 Feb 14;494(7436):247-50 8698195 - Gastroenterology. 1996 Jul;111(1):165-71 7673344 - J Cell Sci. 1995 Jun;108 ( Pt 6):2241-51 16879391 - Histopathology. 2006 Aug;49(2):138-51 16214602 - Lancet. 2005 Oct 8;366(9493):1303-14 |
| References_xml | – volume: 184 start-page: 1263 year: 2014 end-page: 1267 article-title: The liver is a peculiar organ when it comes to stem cells publication-title: Am J Pathol – volume: 41 start-page: 1521 year: 1993 end-page: 1527 article-title: Restricted distribution of integrin beta 6 mRNA in primate epithelial tissues publication-title: J Histochem Cytochem – volume: 49 start-page: 138 year: 2006 end-page: 151 article-title: The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin publication-title: Histopathology – volume: 115 start-page: 2330 year: 2005 end-page: 2340 article-title: TWEAK induces liver progenitor cell proliferation publication-title: J Clin Invest – volume: 15 start-page: 259 year: 1998 end-page: 269 article-title: Ductular reaction and its diagnostic significance publication-title: Semin Diagn Pathol – volume: 96 start-page: 319 year: 1999 end-page: 328 article-title: The integrin alphavbeta6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis publication-title: Cell – volume: 135 start-page: 660 year: 2008 end-page: 670 article-title: Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor‐beta activation and retards biliary fibrosis progression publication-title: Gastroenterology – volume: 41 start-page: 809 year: 2005 end-page: 818 article-title: Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis publication-title: Hepatology – volume: 12 start-page: 410 year: 2006 end-page: 416 article-title: A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells publication-title: Nat Med – volume: 140 start-page: 1642 year: 2011 end-page: 1652 article-title: Tissue transglutaminase does not affect fibrotic matrix stability or regression of liver fibrosis in mice publication-title: Gastroenterology – volume: 271 start-page: 25976 year: 1996 end-page: 25980 article-title: Identification of a sequence within the integrin beta6 subunit cytoplasmic domain that is required to support the specific effect of alphavbeta6 on proliferation in three‐dimensional culture publication-title: J Biol Chem – volume: 52 start-page: 362 year: 2010 end-page: 369 article-title: The alphavbeta6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma publication-title: J Hepatol – volume: 366 start-page: 1303 year: 2005 end-page: 1314 article-title: Cholangiocarcinoma publication-title: Lancet – volume: 13 start-page: 394 year: 2008 end-page: 406 article-title: Regulation of to invasive breast carcinoma transition publication-title: Cancer Cell – volume: 310 start-page: 68 year: 2005 end-page: 71 article-title: Transforming growth factor‐beta signaling in stem cells and cancer publication-title: Science – volume: 59 start-page: 1617 year: 2014 end-page: 1626 article-title: Liver regeneration by stem/progenitor cells publication-title: Hepatology – volume: 111 start-page: 165 year: 1996 end-page: 171 article-title: Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P‐glycoprotein gene publication-title: Gastroenterology – volume: 422 start-page: 169 year: 2003 end-page: 173 article-title: Loss of integrin alpha(v)beta6‐mediated TGF‐beta activation causes Mmp12‐dependent emphysema publication-title: Nature – volume: 61 start-page: 2100 year: 2015 end-page: 2103 article-title: Determining the fate of hepatic cells by lineage tracing: facts and pitfalls publication-title: Hepatology – volume: 25 start-page: 1185 year: 2011 end-page: 1192 article-title: Foxl1‐Cre‐marked adult hepatic progenitors have clonogenic and bilineage differentiation potential publication-title: Genes Dev – volume: 61 start-page: 678 year: 2015 end-page: 691 article-title: Connective tissue growth factor and integrin alphavbeta6: a new pair of regulators critical for ductular reaction and biliary fibrosis in mice publication-title: Hepatology – volume: 31 start-page: 63 year: 2013 end-page: 70 article-title: Mass‐encoded synthetic biomarkers for multiplexed urinary monitoring of disease publication-title: Nat Biotechnol – volume: 171 start-page: 525 year: 2007 end-page: 536 article-title: A new xenobiotic‐induced mouse model of sclerosing cholangitis and biliary fibrosis publication-title: Am J Pathol – volume: 133 start-page: 80 year: 2007 end-page: 90 article-title: Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction publication-title: Gastroenterology – volume: 47 start-page: 1544 year: 2008 end-page: 1556 article-title: Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin publication-title: Hepatology – volume: 147 start-page: 1378 year: 2014 end-page: 1392 article-title: Extrahepatic platelet‐derived growth factor‐beta, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice publication-title: Gastroenterology – volume: 108 start-page: 2241 issue: Pt. 6 year: 1995 end-page: 2251 article-title: Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling publication-title: J Cell Sci – volume: 25 start-page: 1193 year: 2011 end-page: 1203 article-title: Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice publication-title: Genes Dev – volume: 48 start-page: 453 year: 2008 end-page: 464 article-title: Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies publication-title: J Hepatol – volume: 133 start-page: 921 year: 1996 end-page: 928 article-title: Inactivation of the integrin beta6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin publication-title: J Cell Biol – volume: 46 start-page: 1404 year: 2007 end-page: 1412 article-title: Role of alphavbeta6 integrin in acute biliary fibrosis publication-title: Hepatology – volume: 23 start-page: 385 year: 2003 end-page: 396 article-title: Progenitor cells in diseased human liver publication-title: Semin Liver Dis – volume: 51 start-page: 660 year: 2009 end-page: 678 article-title: Diagnosis and management of primary sclerosing cholangitis publication-title: Hepatology – volume: 183 start-page: 182 year: 2013 end-page: 194 article-title: Failure of fibrotic liver regeneration in mice is linked to a severe fibrogenic response driven by hepatic progenitor cell activation publication-title: Am J Pathol – volume: 136 start-page: 1951 year: 2009 end-page: 1960 article-title: Potential hepatic stem cells reside in EpCAM cells of normal and injured mouse liver publication-title: Development – volume: 45 start-page: 226 year: 2004 end-page: 236 article-title: Immunohistochemical screening for beta6‐integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up‐regulation in pancreatic ductal adenocarcinomas and publication-title: Histopathology – volume: 44 start-page: 167 year: 2006 end-page: 175 article-title: Oral imatinib treatment reduces early fibrogenesis but does not prevent progression in the long term publication-title: J Hepatol – volume: 9 start-page: 231 year: 2012 end-page: 240 article-title: The biliary tree—a reservoir of multipotent stem cells publication-title: Nat Rev Gastroenterol Hepatol – volume: 15 start-page: 340 year: 2014 end-page: 349 article-title: Adult hepatocytes are generated by self‐duplication rather than stem cell differentiation publication-title: Cell Stem Cell – volume: 100 start-page: 11881 issue: Suppl. 1 year: 2003 end-page: 11888 article-title: The origin and liver repopulating capacity of murine oval cells publication-title: Proc Natl Acad Sci USA – volume: 50 start-page: 1294 year: 2009 end-page: 1306 article-title: Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies publication-title: Hepatology – volume: 494 start-page: 247 year: 2013 end-page: 250 article-title: expansion of single Lgr5 liver stem cells induced by Wnt‐driven regeneration publication-title: Nature – volume: 185 start-page: 325 year: 2015 end-page: 334 article-title: A new mdr2 mouse model of sclerosing cholangitis with rapid fibrosis progression, early‐onset portal hypertension, and liver cancer publication-title: Am J Pathol – volume: 16 start-page: 295 year: 2009 end-page: 308 article-title: A lymphotoxin‐driven pathway to hepatocellular carcinoma publication-title: Cancer Cell – volume: 45 start-page: 31 year: 2007 end-page: 41 article-title: Transforming growth factor‐beta differentially regulates oval cell and hepatocyte proliferation publication-title: Hepatology – volume: 43 start-page: 1045 year: 2005 end-page: 1054 article-title: Mdr2 (Abcb4) mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro‐ and antifibrogenic genes publication-title: J Hepatol – volume: 474 start-page: 343 year: 2011 end-page: 349 article-title: Latent TGF‐beta structure and activation publication-title: Nature – volume: 279 start-page: 17875 year: 2004 end-page: 17887 article-title: Function‐blocking integrin alphavbeta6 monoclonal antibodies: distinct ligand‐mimetic and nonligand‐mimetic classes publication-title: J Biol Chem – volume: 15 start-page: 605 year: 2014 end-page: 618 article-title: Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes publication-title: Cell Stem Cell – volume: 127 start-page: 1565 year: 2004 end-page: 1577 article-title: The cholangiopathies: disorders of biliary epithelia publication-title: Gastroenterology – volume: 108 start-page: 2241 issue: Pt. 6 year: 1995 ident: hep28274-bib-0010-20241017 article-title: Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling publication-title: J Cell Sci – volume: 494 start-page: 247 year: 2013 ident: hep28274-bib-0049-20241017 article-title: In vitro expansion of single Lgr5+ liver stem cells induced by Wnt‐driven regeneration publication-title: Nature doi: 10.1038/nature11826 – volume: 12 start-page: 410 year: 2006 ident: hep28274-bib-0007-20241017 article-title: A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells publication-title: Nat Med doi: 10.1038/nm1377 – volume: 16 start-page: 295 year: 2009 ident: hep28274-bib-0009-20241017 article-title: A lymphotoxin‐driven pathway to hepatocellular carcinoma publication-title: Cancer Cell doi: 10.1016/j.ccr.2009.08.021 – volume: 45 start-page: 31 year: 2007 ident: hep28274-bib-0044-20241017 article-title: Transforming growth factor‐beta differentially regulates oval cell and hepatocyte proliferation publication-title: Hepatology doi: 10.1002/hep.21466 – volume: 115 start-page: 2330 year: 2005 ident: hep28274-bib-0008-20241017 article-title: TWEAK induces liver progenitor cell proliferation publication-title: J Clin Invest doi: 10.1172/JCI23486 – volume: 111 start-page: 165 year: 1996 ident: hep28274-bib-0025-20241017 article-title: Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P‐glycoprotein gene publication-title: Gastroenterology doi: 10.1053/gast.1996.v111.pm8698195 – volume: 140 start-page: 1642 year: 2011 ident: hep28274-bib-0030-20241017 article-title: Tissue transglutaminase does not affect fibrotic matrix stability or regression of liver fibrosis in mice publication-title: Gastroenterology doi: 10.1053/j.gastro.2011.01.040 – volume: 23 start-page: 385 year: 2003 ident: hep28274-bib-0040-20241017 article-title: Progenitor cells in diseased human liver publication-title: Semin Liver Dis doi: 10.1055/s-2004-815564 – volume: 135 start-page: 660 year: 2008 ident: hep28274-bib-0016-20241017 article-title: Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor‐beta activation and retards biliary fibrosis progression publication-title: Gastroenterology doi: 10.1053/j.gastro.2008.04.009 – volume: 46 start-page: 1404 year: 2007 ident: hep28274-bib-0017-20241017 article-title: Role of alphavbeta6 integrin in acute biliary fibrosis publication-title: Hepatology doi: 10.1002/hep.21849 – volume: 49 start-page: 138 year: 2006 ident: hep28274-bib-0039-20241017 article-title: The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin publication-title: Histopathology doi: 10.1111/j.1365-2559.2006.02468.x – volume: 366 start-page: 1303 year: 2005 ident: hep28274-bib-0002-20241017 article-title: Cholangiocarcinoma publication-title: Lancet doi: 10.1016/S0140-6736(05)67530-7 – volume: 171 start-page: 525 year: 2007 ident: hep28274-bib-0021-20241017 article-title: A new xenobiotic‐induced mouse model of sclerosing cholangitis and biliary fibrosis publication-title: Am J Pathol doi: 10.2353/ajpath.2007.061133 – volume: 184 start-page: 1263 year: 2014 ident: hep28274-bib-0046-20241017 article-title: The liver is a peculiar organ when it comes to stem cells publication-title: Am J Pathol doi: 10.1016/j.ajpath.2014.02.020 – volume: 25 start-page: 1193 year: 2011 ident: hep28274-bib-0029-20241017 article-title: Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice publication-title: Genes Dev doi: 10.1101/gad.2029411 – volume: 279 start-page: 17875 year: 2004 ident: hep28274-bib-0026-20241017 article-title: Function‐blocking integrin alphavbeta6 monoclonal antibodies: distinct ligand‐mimetic and nonligand‐mimetic classes publication-title: J Biol Chem doi: 10.1074/jbc.M312103200 – volume: 43 start-page: 1045 year: 2005 ident: hep28274-bib-0020-20241017 article-title: Mdr2 (Abcb4)−/− mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro‐ and antifibrogenic genes publication-title: J Hepatol doi: 10.1016/j.jhep.2005.06.025 – volume: 474 start-page: 343 year: 2011 ident: hep28274-bib-0012-20241017 article-title: Latent TGF‐beta structure and activation publication-title: Nature doi: 10.1038/nature10152 – volume: 45 start-page: 226 year: 2004 ident: hep28274-bib-0018-20241017 article-title: Immunohistochemical screening for beta6‐integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up‐regulation in pancreatic ductal adenocarcinomas in vivo and in vitro publication-title: Histopathology doi: 10.1111/j.1365-2559.2004.01919.x – volume: 183 start-page: 182 year: 2013 ident: hep28274-bib-0031-20241017 article-title: Failure of fibrotic liver regeneration in mice is linked to a severe fibrogenic response driven by hepatic progenitor cell activation publication-title: Am J Pathol doi: 10.1016/j.ajpath.2013.03.018 – volume: 61 start-page: 2100 year: 2015 ident: hep28274-bib-0047-20241017 article-title: Determining the fate of hepatic cells by lineage tracing: facts and pitfalls publication-title: Hepatology doi: 10.1002/hep.27659 – volume: 9 start-page: 231 year: 2012 ident: hep28274-bib-0036-20241017 article-title: The biliary tree—a reservoir of multipotent stem cells publication-title: Nat Rev Gastroenterol Hepatol doi: 10.1038/nrgastro.2012.23 – volume: 59 start-page: 1617 year: 2014 ident: hep28274-bib-0037-20241017 article-title: Liver regeneration by stem/progenitor cells publication-title: Hepatology doi: 10.1002/hep.26753 – volume: 310 start-page: 68 year: 2005 ident: hep28274-bib-0045-20241017 article-title: Transforming growth factor‐beta signaling in stem cells and cancer publication-title: Science doi: 10.1126/science.1118389 – volume: 185 start-page: 325 year: 2015 ident: hep28274-bib-0032-20241017 article-title: A new mdr2−/− mouse model of sclerosing cholangitis with rapid fibrosis progression, early‐onset portal hypertension, and liver cancer publication-title: Am J Pathol doi: 10.1016/j.ajpath.2014.10.013 – volume: 15 start-page: 259 year: 1998 ident: hep28274-bib-0003-20241017 article-title: Ductular reaction and its diagnostic significance publication-title: Semin Diagn Pathol – volume: 41 start-page: 809 year: 2005 ident: hep28274-bib-0041-20241017 article-title: Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis publication-title: Hepatology doi: 10.1002/hep.20650 – volume: 96 start-page: 319 year: 1999 ident: hep28274-bib-0013-20241017 article-title: The integrin alphavbeta6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis publication-title: Cell doi: 10.1016/S0092-8674(00)80545-0 – volume: 48 start-page: 453 year: 2008 ident: hep28274-bib-0014-20241017 article-title: Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies publication-title: J Hepatol doi: 10.1016/j.jhep.2007.11.021 – volume: 15 start-page: 340 year: 2014 ident: hep28274-bib-0035-20241017 article-title: Adult hepatocytes are generated by self‐duplication rather than stem cell differentiation publication-title: Cell Stem Cell doi: 10.1016/j.stem.2014.06.003 – volume: 13 start-page: 394 year: 2008 ident: hep28274-bib-0028-20241017 article-title: Regulation of in situ to invasive breast carcinoma transition publication-title: Cancer Cell doi: 10.1016/j.ccr.2008.03.007 – volume: 31 start-page: 63 year: 2013 ident: hep28274-bib-0022-20241017 article-title: Mass‐encoded synthetic biomarkers for multiplexed urinary monitoring of disease publication-title: Nat Biotechnol doi: 10.1038/nbt.2464 – volume: 271 start-page: 25976 year: 1996 ident: hep28274-bib-0043-20241017 article-title: Identification of a sequence within the integrin beta6 subunit cytoplasmic domain that is required to support the specific effect of alphavbeta6 on proliferation in three‐dimensional culture publication-title: J Biol Chem doi: 10.1074/jbc.271.42.25976 – volume: 15 start-page: 605 year: 2014 ident: hep28274-bib-0034-20241017 article-title: Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes publication-title: Cell Stem Cell doi: 10.1016/j.stem.2014.09.008 – volume: 50 start-page: 1294 year: 2009 ident: hep28274-bib-0005-20241017 article-title: Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies publication-title: Hepatology doi: 10.1002/hep.23123 – volume: 44 start-page: 167 year: 2006 ident: hep28274-bib-0050-20241017 article-title: Oral imatinib treatment reduces early fibrogenesis but does not prevent progression in the long term publication-title: J Hepatol doi: 10.1016/j.jhep.2005.06.015 – volume: 52 start-page: 362 year: 2010 ident: hep28274-bib-0015-20241017 article-title: The alphavbeta6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma publication-title: J Hepatol doi: 10.1016/j.jhep.2009.12.006 – volume: 61 start-page: 678 year: 2015 ident: hep28274-bib-0019-20241017 article-title: Connective tissue growth factor and integrin alphavbeta6: a new pair of regulators critical for ductular reaction and biliary fibrosis in mice publication-title: Hepatology doi: 10.1002/hep.27425 – volume: 133 start-page: 80 year: 2007 ident: hep28274-bib-0042-20241017 article-title: Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction publication-title: Gastroenterology doi: 10.1053/j.gastro.2007.05.012 – volume: 47 start-page: 1544 year: 2008 ident: hep28274-bib-0006-20241017 article-title: Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin publication-title: Hepatology doi: 10.1002/hep.22238 – volume: 41 start-page: 1521 year: 1993 ident: hep28274-bib-0011-20241017 article-title: Restricted distribution of integrin beta 6 mRNA in primate epithelial tissues publication-title: J Histochem Cytochem doi: 10.1177/41.10.8245410 – volume: 127 start-page: 1565 year: 2004 ident: hep28274-bib-0004-20241017 article-title: The cholangiopathies: disorders of biliary epithelia publication-title: Gastroenterology doi: 10.1053/j.gastro.2004.08.006 – volume: 422 start-page: 169 year: 2003 ident: hep28274-bib-0024-20241017 article-title: Loss of integrin alpha(v)beta6‐mediated TGF‐beta activation causes Mmp12‐dependent emphysema publication-title: Nature doi: 10.1038/nature01413 – volume: 25 start-page: 1185 year: 2011 ident: hep28274-bib-0048-20241017 article-title: Foxl1‐Cre‐marked adult hepatic progenitors have clonogenic and bilineage differentiation potential publication-title: Genes Dev doi: 10.1101/gad.2027811 – volume: 100 start-page: 11881 issue: Suppl. 1 year: 2003 ident: hep28274-bib-0038-20241017 article-title: The origin and liver repopulating capacity of murine oval cells publication-title: Proc Natl Acad Sci USA – volume: 51 start-page: 660 year: 2009 ident: hep28274-bib-0001-20241017 article-title: Diagnosis and management of primary sclerosing cholangitis publication-title: Hepatology – volume: 133 start-page: 921 year: 1996 ident: hep28274-bib-0023-20241017 article-title: Inactivation of the integrin beta6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin publication-title: J Cell Biol doi: 10.1083/jcb.133.4.921 – volume: 147 start-page: 1378 year: 2014 ident: hep28274-bib-0027-20241017 article-title: Extrahepatic platelet‐derived growth factor‐beta, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice publication-title: Gastroenterology doi: 10.1053/j.gastro.2014.08.038 – volume: 136 start-page: 1951 year: 2009 ident: hep28274-bib-0033-20241017 article-title: Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver publication-title: Development doi: 10.1242/dev.031369 – reference: 17924447 - Hepatology. 2007 Nov;46(5):1404-12 – reference: 23354049 - Nature. 2013 Feb 14;494(7436):247-50 – reference: 14722815 - Semin Liver Dis. 2003 Nov;23(4):385-96 – reference: 23242163 - Nat Biotechnol. 2013 Jan;31(1):63-70 – reference: 25203810 - Hepatology. 2015 Feb;61(2):678-91 – reference: 18538673 - Gastroenterology. 2008 Aug;135(2):660-70 – reference: 22371217 - Nat Rev Gastroenterol Hepatol. 2012 Feb 28;9(4):231-40 – reference: 19429791 - Development. 2009 Jun;136(11):1951-60 – reference: 18393293 - Hepatology. 2008 May;47(5):1544-56 – reference: 12634787 - Nature. 2003 Mar 13;422(6928):169-73 – reference: 15521023 - Gastroenterology. 2004 Nov;127(5):1565-77 – reference: 10025398 - Cell. 1999 Feb 5;96(3):319-28 – reference: 20101749 - Hepatology. 2010 Feb;51(2):660-78 – reference: 25503476 - Hepatology. 2015 Jun;61(6):2100-3 – reference: 12902545 - Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11881-8 – reference: 21677751 - Nature. 2011 Jun 15;474(7351):343-9 – reference: 25478810 - Am J Pathol. 2015 Feb;185(2):325-34 – reference: 9845427 - Semin Diagn Pathol. 1998 Nov;15(4):259-69 – reference: 20137822 - J Hepatol. 2010 Mar;52(3):362-9 – reference: 23680654 - Am J Pathol. 2013 Jul;183(1):182-94 – reference: 24681248 - Am J Pathol. 2014 May;184(5):1263-7 – reference: 25130492 - Cell Stem Cell. 2014 Sep 4;15(3):340-9 – reference: 14960589 - J Biol Chem. 2004 Apr 23;279(17 ):17875-87 – reference: 7673344 - J Cell Sci. 1995 Jun;108 ( Pt 6):2241-51 – reference: 17600122 - Am J Pathol. 2007 Aug;171(2):525-36 – reference: 21632826 - Genes Dev. 2011 Jun 1;25(11):1193-203 – reference: 25312494 - Cell Stem Cell. 2014 Nov 6;15(5):605-18 – reference: 19800575 - Cancer Cell. 2009 Oct 6;16(4):295-308 – reference: 8698195 - Gastroenterology. 1996 Jul;111(1):165-71 – reference: 25173753 - Gastroenterology. 2014 Dec;147(6):1378-92 – reference: 8824234 - J Biol Chem. 1996 Oct 18;271(42):25976-80 – reference: 17631134 - Gastroenterology. 2007 Jul;133(1):80-90 – reference: 21632825 - Genes Dev. 2011 Jun 1;25(11):1185-92 – reference: 15793848 - Hepatology. 2005 Apr;41(4):809-18 – reference: 16532004 - Nat Med. 2006 Apr;12(4):410-6 – reference: 16110324 - J Clin Invest. 2005 Sep;115(9):2330-40 – reference: 16879391 - Histopathology. 2006 Aug;49(2):138-51 – reference: 16210527 - Science. 2005 Oct 7;310(5745):68-71 – reference: 15330800 - Histopathology. 2004 Sep;45(3):226-36 – reference: 8245410 - J Histochem Cytochem. 1993 Oct;41(10):1521-7 – reference: 8666675 - J Cell Biol. 1996 May;133(4):921-8 – reference: 18455123 - Cancer Cell. 2008 May;13(5):394-406 – reference: 16214602 - Lancet. 2005 Oct 8;366(9493):1303-14 – reference: 21277850 - Gastroenterology. 2011 May;140(5):1642-52 – reference: 18221819 - J Hepatol. 2008 Mar;48(3):453-64 – reference: 17187411 - Hepatology. 2007 Jan;45(1):31-41 – reference: 24115180 - Hepatology. 2014 Apr;59(4):1617-26 – reference: 16168515 - J Hepatol. 2006 Jan;44(1):167-75 – reference: 16223543 - J Hepatol. 2005 Dec;43(6):1045-54 – reference: 19711424 - Hepatology. 2009 Oct;50(4):1294-306 |
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| SubjectTerms | Animals Antigens, Neoplasm - physiology Carcinogenesis Cholangitis, Sclerosing - etiology Fibrosis - etiology Hepatocytes Humans Integrins - physiology Liver - pathology Liver Cirrhosis - etiology Liver Neoplasms - etiology Male Mice Mice, Inbred C57BL Stem Cells - physiology |
| Title | Integrin αvβ6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis |
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