Gli signaling pathway modulates fibroblast activation and facilitates scar formation in pulmonary fibrosis

Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually respiratory failure. The precise mechanism of alveolar scarring is poorly understood. In this study, we explored transcriptional signatures of act...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Biochemical and biophysical research communications Ročník 514; číslo 3; s. 684 - 690
Hlavní autori:	Tsukui, Tatsuya, Ueha, Satoshi, Shichino, Shigeyuki, Hashimoto, Shinichi, Nakajima, Takuya, Shiraishi, Kazushige, Kihara, Miho, Kiyonari, Hiroshi, Inagaki, Yutaka, Matsushima, Kouji
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Elsevier Inc 30.06.2019
Predmet:	epithelium extracellular matrix Fibroblasts fibrosis GANT61 gene expression regulation Gli pathway lungs metabolism mice oncogenes Pulmonary fibrosis Scar signal transduction transcription (genetics) transcription factors translation (genetics) Wound healing BLM Wound healing Gli Scar ECM α-SMA mKO1 Pulmonary fibrosis Col-GFP Fibroblasts Gli pathway GANT61 IPF
ISSN:	0006-291X, 1090-2104, 1090-2104
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually respiratory failure. The precise mechanism of alveolar scarring is poorly understood. In this study, we explored transcriptional signatures of activated fibroblasts in alveolar airspaces by using intratracheal transfer in bleomycin-induced lung fibrosis. Lung fibroblasts transferred into injured alveoli upregulated genes related to translation and metabolism in the first two days, and upregulated genes related to extracellular matrix (ECM) production between day 2 and 7. Upstream analysis of these upregulated genes suggested possible contribution of hypoxia-inducible factors 1a (Hif1a) to fibroblast activation in the first two days, and possible contribution of kruppel-like factor 4 (Klf4) and glioma-associated oncogene (Gli) transcription factors to fibroblast activation in the following profibrotic phase. Fibroblasts purified based on high Acta2 expression after intratracheal transfer were also characterized by ECM production and upstream regulation by Klf4 and Gli proteins. Pharmacological inhibition of Gli proteins by GANT61 in bleomycin-induced lung fibrosis altered the pattern of scarring characterized by dilated airspaces and smaller fibroblast clusters. Activated fibroblasts isolated from GANT61-treated mice showed decreased migration capacity, suggesting that Gli signaling inhibition attenuated fibroblast activation. In conclusion, we revealed transcriptional signatures and possible upstream regulators of activated fibroblasts in injured alveolar airspaces. The altered scar formation by Gli signaling inhibition supports that activated fibroblasts in alveolar airspaces may play a critical role in scar formation. •Hif1a is an initial gene regulator in fibroblasts exposed to injured alveolar airspaces.•Klf4 and Gli proteins may subsequently upregulate ECM genes in activated fibroblasts.•Pharmacological inhibition of Gli signalings in lung fibrosis alters scar formation.•Gli signaling inhibition reduces migration capacity of fibroblasts in fibrotic lungs.
AbstractList	Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually respiratory failure. The precise mechanism of alveolar scarring is poorly understood. In this study, we explored transcriptional signatures of activated fibroblasts in alveolar airspaces by using intratracheal transfer in bleomycin-induced lung fibrosis. Lung fibroblasts transferred into injured alveoli upregulated genes related to translation and metabolism in the first two days, and upregulated genes related to extracellular matrix (ECM) production between day 2 and 7. Upstream analysis of these upregulated genes suggested possible contribution of hypoxia-inducible factors 1a (Hif1a) to fibroblast activation in the first two days, and possible contribution of kruppel-like factor 4 (Klf4) and glioma-associated oncogene (Gli) transcription factors to fibroblast activation in the following profibrotic phase. Fibroblasts purified based on high Acta2 expression after intratracheal transfer were also characterized by ECM production and upstream regulation by Klf4 and Gli proteins. Pharmacological inhibition of Gli proteins by GANT61 in bleomycin-induced lung fibrosis altered the pattern of scarring characterized by dilated airspaces and smaller fibroblast clusters. Activated fibroblasts isolated from GANT61-treated mice showed decreased migration capacity, suggesting that Gli signaling inhibition attenuated fibroblast activation. In conclusion, we revealed transcriptional signatures and possible upstream regulators of activated fibroblasts in injured alveolar airspaces. The altered scar formation by Gli signaling inhibition supports that activated fibroblasts in alveolar airspaces may play a critical role in scar formation.Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually respiratory failure. The precise mechanism of alveolar scarring is poorly understood. In this study, we explored transcriptional signatures of activated fibroblasts in alveolar airspaces by using intratracheal transfer in bleomycin-induced lung fibrosis. Lung fibroblasts transferred into injured alveoli upregulated genes related to translation and metabolism in the first two days, and upregulated genes related to extracellular matrix (ECM) production between day 2 and 7. Upstream analysis of these upregulated genes suggested possible contribution of hypoxia-inducible factors 1a (Hif1a) to fibroblast activation in the first two days, and possible contribution of kruppel-like factor 4 (Klf4) and glioma-associated oncogene (Gli) transcription factors to fibroblast activation in the following profibrotic phase. Fibroblasts purified based on high Acta2 expression after intratracheal transfer were also characterized by ECM production and upstream regulation by Klf4 and Gli proteins. Pharmacological inhibition of Gli proteins by GANT61 in bleomycin-induced lung fibrosis altered the pattern of scarring characterized by dilated airspaces and smaller fibroblast clusters. Activated fibroblasts isolated from GANT61-treated mice showed decreased migration capacity, suggesting that Gli signaling inhibition attenuated fibroblast activation. In conclusion, we revealed transcriptional signatures and possible upstream regulators of activated fibroblasts in injured alveolar airspaces. The altered scar formation by Gli signaling inhibition supports that activated fibroblasts in alveolar airspaces may play a critical role in scar formation. Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually respiratory failure. The precise mechanism of alveolar scarring is poorly understood. In this study, we explored transcriptional signatures of activated fibroblasts in alveolar airspaces by using intratracheal transfer in bleomycin-induced lung fibrosis. Lung fibroblasts transferred into injured alveoli upregulated genes related to translation and metabolism in the first two days, and upregulated genes related to extracellular matrix (ECM) production between day 2 and 7. Upstream analysis of these upregulated genes suggested possible contribution of hypoxia-inducible factors 1a (Hif1a) to fibroblast activation in the first two days, and possible contribution of kruppel-like factor 4 (Klf4) and glioma-associated oncogene (Gli) transcription factors to fibroblast activation in the following profibrotic phase. Fibroblasts purified based on high Acta2 expression after intratracheal transfer were also characterized by ECM production and upstream regulation by Klf4 and Gli proteins. Pharmacological inhibition of Gli proteins by GANT61 in bleomycin-induced lung fibrosis altered the pattern of scarring characterized by dilated airspaces and smaller fibroblast clusters. Activated fibroblasts isolated from GANT61-treated mice showed decreased migration capacity, suggesting that Gli signaling inhibition attenuated fibroblast activation. In conclusion, we revealed transcriptional signatures and possible upstream regulators of activated fibroblasts in injured alveolar airspaces. The altered scar formation by Gli signaling inhibition supports that activated fibroblasts in alveolar airspaces may play a critical role in scar formation. Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually respiratory failure. The precise mechanism of alveolar scarring is poorly understood. In this study, we explored transcriptional signatures of activated fibroblasts in alveolar airspaces by using intratracheal transfer in bleomycin-induced lung fibrosis. Lung fibroblasts transferred into injured alveoli upregulated genes related to translation and metabolism in the first two days, and upregulated genes related to extracellular matrix (ECM) production between day 2 and 7. Upstream analysis of these upregulated genes suggested possible contribution of hypoxia-inducible factors 1a (Hif1a) to fibroblast activation in the first two days, and possible contribution of kruppel-like factor 4 (Klf4) and glioma-associated oncogene (Gli) transcription factors to fibroblast activation in the following profibrotic phase. Fibroblasts purified based on high Acta2 expression after intratracheal transfer were also characterized by ECM production and upstream regulation by Klf4 and Gli proteins. Pharmacological inhibition of Gli proteins by GANT61 in bleomycin-induced lung fibrosis altered the pattern of scarring characterized by dilated airspaces and smaller fibroblast clusters. Activated fibroblasts isolated from GANT61-treated mice showed decreased migration capacity, suggesting that Gli signaling inhibition attenuated fibroblast activation. In conclusion, we revealed transcriptional signatures and possible upstream regulators of activated fibroblasts in injured alveolar airspaces. The altered scar formation by Gli signaling inhibition supports that activated fibroblasts in alveolar airspaces may play a critical role in scar formation. •Hif1a is an initial gene regulator in fibroblasts exposed to injured alveolar airspaces.•Klf4 and Gli proteins may subsequently upregulate ECM genes in activated fibroblasts.•Pharmacological inhibition of Gli signalings in lung fibrosis alters scar formation.•Gli signaling inhibition reduces migration capacity of fibroblasts in fibrotic lungs.
Author	Ueha, Satoshi Shichino, Shigeyuki Kihara, Miho Nakajima, Takuya Shiraishi, Kazushige Kiyonari, Hiroshi Hashimoto, Shinichi Tsukui, Tatsuya Inagaki, Yutaka Matsushima, Kouji
Author_xml	– sequence: 1 givenname: Tatsuya orcidid: 0000-0003-3100-6934 surname: Tsukui fullname: Tsukui, Tatsuya organization: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 2 givenname: Satoshi surname: Ueha fullname: Ueha, Satoshi organization: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 3 givenname: Shigeyuki surname: Shichino fullname: Shichino, Shigeyuki organization: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 4 givenname: Shinichi surname: Hashimoto fullname: Hashimoto, Shinichi organization: Japan Agency for Medical Research and Development-CREST Program, Tokyo, Japan – sequence: 5 givenname: Takuya surname: Nakajima fullname: Nakajima, Takuya organization: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 6 givenname: Kazushige orcidid: 0000-0001-6510-7157 surname: Shiraishi fullname: Shiraishi, Kazushige organization: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan – sequence: 7 givenname: Miho surname: Kihara fullname: Kihara, Miho organization: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan – sequence: 8 givenname: Hiroshi surname: Kiyonari fullname: Kiyonari, Hiroshi organization: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan – sequence: 9 givenname: Yutaka surname: Inagaki fullname: Inagaki, Yutaka organization: Japan Agency for Medical Research and Development-CREST Program, Tokyo, Japan – sequence: 10 givenname: Kouji surname: Matsushima fullname: Matsushima, Kouji email: koujim@rs.tus.ac.jp organization: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/31078262$$D View this record in MEDLINE/PubMed
BookMark	eNqNkT1v1TAUhi3Uit4W_gADysiScOwkjiOxoIoWpEosRWKz_HFSfOU4F9sp6r-vL2kXhorJg5_nlc77npOTsAQk5B2FhgLlH_eN1tE0DOjYQN8Apa_IjsIINaPQnZAdAPCajfTnGTlPaQ-F6Pj4mpy1FAbBONuR_bV3VXJ3QXkX7qqDyr_-qIdqXuzqVcZUTU7HRXuVcqVMdvcquyVUKthqUsZ5l_9SyahYTUuct28XqsPq5yWo-LAlJJfekNNJ-YRvn94L8uPqy-3l1_rm-_W3y883ten6Ptd0sBo0Uzhq07VMtWhQwMCHgRorFDIt0GoBjE4TRWt7NnDFpgGFKgiH9oJ82HIPcfm9Yspydsmg9yrgsibJmOAjFdAP_4G2dOSia3lB3z-hq57RykN0c7lOPldZALEBplybIk7SHMspdeSonJcU5HE1uZfH1eRxNQm9LJsUlf2jPqe_KH3aJCxd3juMMhmHwaB1EU2WdnEv6Y9Wb7J7
CitedBy_id	crossref_primary_10_1038_s41597_021_01063_x crossref_primary_10_1038_s41467_020_15647_5 crossref_primary_10_1172_JCI165836 crossref_primary_10_1515_hsz_2020_0125 crossref_primary_10_1089_jop_2023_0022
Cites_doi	10.1183/16000617.0062-2017 10.1096/fj.201600892RR 10.1136/annrheumdis-2016-209698 10.1016/j.ajpath.2015.07.022 10.1161/01.RES.84.7.852 10.1172/JCI74929 10.1016/j.ajpath.2015.07.013 10.1016/j.ajpath.2013.06.005 10.1016/S0140-6736(11)60052-4 10.1164/rccm.201403-0509PP 10.1038/nrm3598 10.1165/rcmb.2013-0154OC 10.1165/rcmb.2014-0132TR 10.3389/fphar.2017.00326 10.1126/science.1203165 10.1371/journal.pone.0069128 10.1172/JCI99435 10.1016/j.celrep.2015.11.005 10.1038/nature07039 10.1002/j.2040-4603.2016.tb00698.x 10.1038/nrm809 10.1053/j.gastro.2009.07.006 10.1165/rcmb.2012-0347OC
ContentType	Journal Article
Copyright	2019 Elsevier Inc. Copyright © 2019 Elsevier Inc. All rights reserved.
Copyright_xml	– notice: 2019 Elsevier Inc. – notice: Copyright © 2019 Elsevier Inc. All rights reserved.
DBID	AAYXX CITATION NPM 7X8 7S9 L.6
DOI	10.1016/j.bbrc.2019.05.011
DatabaseName	CrossRef PubMed MEDLINE - Academic AGRICOLA AGRICOLA - Academic
DatabaseTitle	CrossRef PubMed MEDLINE - Academic AGRICOLA AGRICOLA - Academic
DatabaseTitleList	MEDLINE - Academic PubMed AGRICOLA
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Anatomy & Physiology Chemistry Biology
EISSN	1090-2104
EndPage	690
ExternalDocumentID	31078262 10_1016_j_bbrc_2019_05_011 S0006291X19308794
Genre	Journal Article
GroupedDBID	--- --K --M -~X .~1 0R~ 1B1 1RT 1~. 1~5 23N 4.4 457 4G. 53G 5GY 5VS 6J9 7-5 71M 8P~ 9JM AABNK AACTN AAEDT AAEDW AAHBH AAIAV AAIKJ AAKOC AALRI AAOAW AAQFI AAXUO ABFNM ABFRF ABGSF ABJNI ABMAC ABUDA ACDAQ ACGFO ACGFS ACNCT ACRLP ADBBV ADEZE ADUVX AEBSH AEFWE AEHWI AEKER AENEX AFFNX AFKWA AFTJW AFXIZ AGHFR AGUBO AGYEJ AIEXJ AIKHN AITUG AJOXV AKRWK ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ AXJTR BKOJK BLXMC CS3 D0L DM4 EBS EFBJH EJD EO8 EO9 EP2 EP3 F5P FDB FIRID FNPLU FYGXN G-Q GBLVA IHE J1W K-O KOM L7B LG5 LX2 M41 MO0 N9A O-L O9- OAUVE OZT P-8 P-9 P2P PC. Q38 RIG RNS ROL RPZ SCC SDF SDG SDP SES SPCBC SSU SSZ T5K TWZ WH7 XPP XSW ZA5 ZMT ~02 ~G- .55 .GJ .HR 1CY 3O- 9DU 9M8 AAQXK AATTM AAXKI AAYJJ AAYWO AAYXX ABDPE ABEFU ABWVN ABXDB ACKIV ACLOT ACRPL ACVFH ADCNI ADFGL ADIYS ADMUD ADNMO AEIPS AEUPX AFJKZ AFPUW AGQPQ AGRDE AHHHB AIGII AIIUN AKBMS AKYEP ANKPU APXCP ASPBG AVWKF AZFZN CAG CITATION COF EFKBS EFLBG FEDTE FGOYB G-2 HLW HVGLF HZ~ MVM OHT R2- SBG SEW UQL WUQ X7M Y6R ZGI ZKB ~HD ~KM NPM SSH 7X8 7S9 L.6
ID	FETCH-LOGICAL-c455t-17db0b2ae9bc432a3ece8076771cd8ae2b8edb8021ff1edd5276a2f7e8a771603
ISICitedReferencesCount	5
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000470803000019&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	0006-291X 1090-2104
IngestDate	Sun Sep 28 10:16:52 EDT 2025 Thu Oct 02 14:35:31 EDT 2025 Thu Apr 03 07:04:58 EDT 2025 Sat Nov 29 06:56:57 EST 2025 Tue Nov 18 20:49:47 EST 2025 Sat Jul 06 15:30:19 EDT 2024
IsPeerReviewed	true
IsScholarly	true
Issue	3
Keywords	BLM Wound healing Gli Scar ECM α-SMA mKO1 Pulmonary fibrosis Col-GFP Fibroblasts Gli pathway GANT61 IPF
Language	English
License	Copyright © 2019 Elsevier Inc. All rights reserved.
LinkModel	OpenURL
MergedId	FETCHMERGED-LOGICAL-c455t-17db0b2ae9bc432a3ece8076771cd8ae2b8edb8021ff1edd5276a2f7e8a771603
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ORCID	0000-0003-3100-6934 0000-0001-6510-7157
PMID	31078262
PQID	2231968436
PQPubID	23479
PageCount	7
ParticipantIDs	proquest_miscellaneous_2286918057 proquest_miscellaneous_2231968436 pubmed_primary_31078262 crossref_citationtrail_10_1016_j_bbrc_2019_05_011 crossref_primary_10_1016_j_bbrc_2019_05_011 elsevier_sciencedirect_doi_10_1016_j_bbrc_2019_05_011
PublicationCentury	2000
PublicationDate	2019-06-30
PublicationDateYYYYMMDD	2019-06-30
PublicationDate_xml	– month: 06 year: 2019 text: 2019-06-30 day: 30
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Biochemical and biophysical research communications
PublicationTitleAlternate	Biochem Biophys Res Commun
PublicationYear	2019
Publisher	Elsevier Inc
Publisher_xml	– name: Elsevier Inc
References	Kim, Wessling-Resnick (bib21) 2012; 3 King, Pardo, Selman (bib1) 2011; 378 Tomasek, Gabbiani, Hinz, Chaponnier, Brown (bib4) 2002; 3 Wang, de Mochel, Christenson, Cassandras, Moon, Brumwell, Byrnes, Li, Yokosaki, Shan, Sneddon, Jablons, Lee, Matthay, Chapman, Peng (bib25) 2018; 128 Plantier, Cazes, Dinh-Xuan, Bancal, Marchand-Adam, Crestani (bib3) 2018; 27 Kramann, Fleig, Schneider, Fabian, DiRocco, Maarouf, Wongboonsin, Ikeda, Heckl, Chang, Rennke, Waikar, Humphreys (bib9) 2015; 125 Mack, Owens (bib13) 1999; 84 Liang, Sumova, Cordazzo, Mallano, Zhang, Wohlfahrt, Dees, Ramming, Krasowska, Michalska-Jakubus, Distler, Schett, Senolt, Distler (bib10) 2017; 76 Hsia, Hyde, Weibel (bib2) 2016; 6 Tsukui, Ueha, Shichino, Inagaki, Matsushima (bib6) 2015; 185 Kugler, Joyner, Loomis, Munger (bib22) 2015; 52 Tsukui, Ueha, Abe, Hashimoto, Shichino, Shimaoka, Shand, Arakawa, Oshima, Hattori, Inagaki, Tomura, Matsushima (bib14) 2013; 183 Goritz, Dias, Tomilin, Barbacid, Shupliakov, Frisen (bib7) 2011; 333 Ahluwalia, Shea, Tager (bib5) 2014; 190 Vogler, Vogel, Krull, Farhat, Leisering, Lutz, Wuertz, Katschinski, Zieseniss (bib19) 2013; 8 Shichino, Abe, Ueha, Otsuji, Tsukui, Kosugi-Kanaya, Shand, Hashimoto, Suzuki, Morikawa, Inagaki, Matsushima (bib15) 2015; 185 Xiong, Liu (bib18) 2017; 8 Shichino, Ueha, Hashimoto, Otsuji, Abe, Tsukui, Deshimaru, Nakajima, Kosugi-Kanaya, Shand, Inagaki, Shimano, Matsushima (bib16) 2019 Liu, Kugler, Loomis, Samdani, Zhao, Chen, Brandt, Brownell, Joyner, Rom, Munger (bib24) 2013; 48 Gurtner, Werner, Barrandon, Longaker (bib23) 2008; 453 Siegert, Schodel, Nairz, Schatz, Dettmer, Dick, Kalucka, Franke, Ehrenschwender, Schley, Beneke, Sutter, Moll, Hellerbrand, Wielockx, Katschinski, Lang, Galy, Hentze, Koivunen, Oefner, Bogdan, Weiss, Willam, Jantsch (bib20) 2015; 13 Higashiyama, Moro, Nakao, Mikami, Fukumitsu, Ueda, Ikeda, Adachi, Bou–Gharios, Okazaki, Inagaki (bib12) 2009; 137 Briscoe, Therond (bib8) 2013; 14 Didiasova, Singh, Wilhelm, Kwapiszewska, Wujak, Zakrzewicz, Schaefer, Markart, Seeger, Lauth, Wygrecka (bib11) 2017; 31 Moshai, Wemeau-Stervinou, Cigna, Brayer, Somme, Crestani, Mailleux (bib17) 2014; 51 Xiong (10.1016/j.bbrc.2019.05.011_bib18) 2017; 8 Tsukui (10.1016/j.bbrc.2019.05.011_bib14) 2013; 183 Didiasova (10.1016/j.bbrc.2019.05.011_bib11) 2017; 31 Shichino (10.1016/j.bbrc.2019.05.011_bib16) 2019 King (10.1016/j.bbrc.2019.05.011_bib1) 2011; 378 Briscoe (10.1016/j.bbrc.2019.05.011_bib8) 2013; 14 Ahluwalia (10.1016/j.bbrc.2019.05.011_bib5) 2014; 190 Siegert (10.1016/j.bbrc.2019.05.011_bib20) 2015; 13 Gurtner (10.1016/j.bbrc.2019.05.011_bib23) 2008; 453 Kramann (10.1016/j.bbrc.2019.05.011_bib9) 2015; 125 Plantier (10.1016/j.bbrc.2019.05.011_bib3) 2018; 27 Liu (10.1016/j.bbrc.2019.05.011_bib24) 2013; 48 Higashiyama (10.1016/j.bbrc.2019.05.011_bib12) 2009; 137 Tsukui (10.1016/j.bbrc.2019.05.011_bib6) 2015; 185 Goritz (10.1016/j.bbrc.2019.05.011_bib7) 2011; 333 Kim (10.1016/j.bbrc.2019.05.011_bib21) 2012; 3 Hsia (10.1016/j.bbrc.2019.05.011_bib2) 2016; 6 Vogler (10.1016/j.bbrc.2019.05.011_bib19) 2013; 8 Tomasek (10.1016/j.bbrc.2019.05.011_bib4) 2002; 3 Wang (10.1016/j.bbrc.2019.05.011_bib25) 2018; 128 Kugler (10.1016/j.bbrc.2019.05.011_bib22) 2015; 52 Liang (10.1016/j.bbrc.2019.05.011_bib10) 2017; 76 Moshai (10.1016/j.bbrc.2019.05.011_bib17) 2014; 51 Shichino (10.1016/j.bbrc.2019.05.011_bib15) 2015; 185 Mack (10.1016/j.bbrc.2019.05.011_bib13) 1999; 84
References_xml	– volume: 8 start-page: 326 year: 2017 ident: bib18 article-title: Targeting hypoxia inducible factors-1alpha as a novel therapy in fibrosis publication-title: Front. Pharmacol. – volume: 8 year: 2013 ident: bib19 article-title: Hypoxia modulates fibroblastic architecture, adhesion and migration: a role for HIF-1alpha in cofilin regulation and cytoplasmic actin distribution publication-title: PLoS One – volume: 84 start-page: 852 year: 1999 end-page: 861 ident: bib13 article-title: Regulation of smooth muscle alpha-actin expression in vivo is dependent on CArG elements within the 5' and first intron promoter regions publication-title: Circ. Res. – volume: 378 start-page: 1949 year: 2011 end-page: 1961 ident: bib1 article-title: Idiopathic pulmonary fibrosis publication-title: Lancet – volume: 14 start-page: 416 year: 2013 end-page: 429 ident: bib8 article-title: The mechanisms of Hedgehog signalling and its roles in development and disease publication-title: Nat. Rev. Mol. Cell Biol. – volume: 183 start-page: 758 year: 2013 end-page: 773 ident: bib14 article-title: Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis publication-title: Am. J. Pathol. – volume: 31 start-page: 1916 year: 2017 end-page: 1928 ident: bib11 article-title: Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors publication-title: FASEB J. – volume: 6 start-page: 827 year: 2016 end-page: 895 ident: bib2 article-title: Lung structure and the intrinsic challenges of gas exchange publication-title: Comp. Physiol. – volume: 190 start-page: 867 year: 2014 end-page: 878 ident: bib5 article-title: New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses publication-title: Am. J. Respir. Crit. Care Med. – volume: 51 start-page: 11 year: 2014 end-page: 25 ident: bib17 article-title: Targeting the hedgehog-glioma-associated oncogene homolog pathway inhibits bleomycin-induced lung fibrosis in mice publication-title: Am. J. Respir. Cell Mol. Biol. – volume: 333 start-page: 238 year: 2011 end-page: 242 ident: bib7 article-title: A pericyte origin of spinal cord scar tissue publication-title: Science – volume: 137 start-page: 1459 year: 2009 end-page: 1466 ident: bib12 article-title: Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice publication-title: Gastroenterology – volume: 27 year: 2018 ident: bib3 article-title: Physiology of the lung in idiopathic pulmonary fibrosis publication-title: Eur. Respir. Rev. – volume: 453 start-page: 314 year: 2008 end-page: 321 ident: bib23 article-title: Wound repair and regeneration publication-title: Nature – volume: 185 start-page: 2923 year: 2015 end-page: 2938 ident: bib15 article-title: Reduced supply of monocyte-derived macrophages leads to a transition from nodular to diffuse lesions and tissue cell activation in silica-induced pulmonary fibrosis in mice publication-title: Am. J. Pathol. – volume: 52 start-page: 1 year: 2015 end-page: 13 ident: bib22 article-title: Sonic hedgehog signaling in the lung. From development to disease publication-title: Am. J. Respir. Cell Mol. Biol. – volume: 185 start-page: 2939 year: 2015 end-page: 2948 ident: bib6 article-title: Intratracheal cell transfer demonstrates the profibrotic potential of resident fibroblasts in pulmonary fibrosis publication-title: Am. J. Pathol. – volume: 48 start-page: 703 year: 2013 end-page: 710 ident: bib24 article-title: Hedgehog signaling in neonatal and adult lung publication-title: Am. J. Respir. Cell Mol. Biol. – volume: 3 year: 2012 ident: bib21 article-title: The role of iron metabolism in lung inflammation and injury publication-title: J. Allergy Ther. – volume: 76 start-page: 756 year: 2017 end-page: 764 ident: bib10 article-title: The transcription factor GLI2 as a downstream mediator of transforming growth factor-beta-induced fibroblast activation in SSc publication-title: Ann. Rheum. Dis. – start-page: 4 year: 2019 ident: bib16 article-title: Transcriptome network analysis identifies protective role of the LXR/SREBP-1c axis in murine pulmonary fibrosis publication-title: JCI Insight – volume: 13 start-page: 2048 year: 2015 end-page: 2055 ident: bib20 article-title: Ferritin-mediated iron sequestration stabilizes hypoxia-inducible factor-1alpha upon LPS activation in the presence of ample oxygen publication-title: Cell Rep. – volume: 125 start-page: 2935 year: 2015 end-page: 2951 ident: bib9 article-title: Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis publication-title: J. Clin. Investig. – volume: 128 start-page: 4343 year: 2018 end-page: 4358 ident: bib25 article-title: Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype publication-title: J. Clin. Investig. – volume: 3 start-page: 349 year: 2002 end-page: 363 ident: bib4 article-title: Myofibroblasts and mechano-regulation of connective tissue remodelling publication-title: Nat. Rev. Mol. Cell Biol. – volume: 27 year: 2018 ident: 10.1016/j.bbrc.2019.05.011_bib3 article-title: Physiology of the lung in idiopathic pulmonary fibrosis publication-title: Eur. Respir. Rev. doi: 10.1183/16000617.0062-2017 – volume: 31 start-page: 1916 year: 2017 ident: 10.1016/j.bbrc.2019.05.011_bib11 article-title: Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors publication-title: FASEB J. doi: 10.1096/fj.201600892RR – volume: 76 start-page: 756 year: 2017 ident: 10.1016/j.bbrc.2019.05.011_bib10 article-title: The transcription factor GLI2 as a downstream mediator of transforming growth factor-beta-induced fibroblast activation in SSc publication-title: Ann. Rheum. Dis. doi: 10.1136/annrheumdis-2016-209698 – volume: 185 start-page: 2939 year: 2015 ident: 10.1016/j.bbrc.2019.05.011_bib6 article-title: Intratracheal cell transfer demonstrates the profibrotic potential of resident fibroblasts in pulmonary fibrosis publication-title: Am. J. Pathol. doi: 10.1016/j.ajpath.2015.07.022 – volume: 84 start-page: 852 year: 1999 ident: 10.1016/j.bbrc.2019.05.011_bib13 article-title: Regulation of smooth muscle alpha-actin expression in vivo is dependent on CArG elements within the 5' and first intron promoter regions publication-title: Circ. Res. doi: 10.1161/01.RES.84.7.852 – volume: 125 start-page: 2935 year: 2015 ident: 10.1016/j.bbrc.2019.05.011_bib9 article-title: Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis publication-title: J. Clin. Investig. doi: 10.1172/JCI74929 – volume: 185 start-page: 2923 year: 2015 ident: 10.1016/j.bbrc.2019.05.011_bib15 article-title: Reduced supply of monocyte-derived macrophages leads to a transition from nodular to diffuse lesions and tissue cell activation in silica-induced pulmonary fibrosis in mice publication-title: Am. J. Pathol. doi: 10.1016/j.ajpath.2015.07.013 – volume: 183 start-page: 758 year: 2013 ident: 10.1016/j.bbrc.2019.05.011_bib14 article-title: Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis publication-title: Am. J. Pathol. doi: 10.1016/j.ajpath.2013.06.005 – volume: 3 year: 2012 ident: 10.1016/j.bbrc.2019.05.011_bib21 article-title: The role of iron metabolism in lung inflammation and injury publication-title: J. Allergy Ther. – volume: 378 start-page: 1949 year: 2011 ident: 10.1016/j.bbrc.2019.05.011_bib1 article-title: Idiopathic pulmonary fibrosis publication-title: Lancet doi: 10.1016/S0140-6736(11)60052-4 – volume: 190 start-page: 867 year: 2014 ident: 10.1016/j.bbrc.2019.05.011_bib5 article-title: New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses publication-title: Am. J. Respir. Crit. Care Med. doi: 10.1164/rccm.201403-0509PP – volume: 14 start-page: 416 year: 2013 ident: 10.1016/j.bbrc.2019.05.011_bib8 article-title: The mechanisms of Hedgehog signalling and its roles in development and disease publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm3598 – start-page: 4 year: 2019 ident: 10.1016/j.bbrc.2019.05.011_bib16 article-title: Transcriptome network analysis identifies protective role of the LXR/SREBP-1c axis in murine pulmonary fibrosis publication-title: JCI Insight – volume: 51 start-page: 11 year: 2014 ident: 10.1016/j.bbrc.2019.05.011_bib17 article-title: Targeting the hedgehog-glioma-associated oncogene homolog pathway inhibits bleomycin-induced lung fibrosis in mice publication-title: Am. J. Respir. Cell Mol. Biol. doi: 10.1165/rcmb.2013-0154OC – volume: 52 start-page: 1 year: 2015 ident: 10.1016/j.bbrc.2019.05.011_bib22 article-title: Sonic hedgehog signaling in the lung. From development to disease publication-title: Am. J. Respir. Cell Mol. Biol. doi: 10.1165/rcmb.2014-0132TR – volume: 8 start-page: 326 year: 2017 ident: 10.1016/j.bbrc.2019.05.011_bib18 article-title: Targeting hypoxia inducible factors-1alpha as a novel therapy in fibrosis publication-title: Front. Pharmacol. doi: 10.3389/fphar.2017.00326 – volume: 333 start-page: 238 year: 2011 ident: 10.1016/j.bbrc.2019.05.011_bib7 article-title: A pericyte origin of spinal cord scar tissue publication-title: Science doi: 10.1126/science.1203165 – volume: 8 year: 2013 ident: 10.1016/j.bbrc.2019.05.011_bib19 article-title: Hypoxia modulates fibroblastic architecture, adhesion and migration: a role for HIF-1alpha in cofilin regulation and cytoplasmic actin distribution publication-title: PLoS One doi: 10.1371/journal.pone.0069128 – volume: 128 start-page: 4343 year: 2018 ident: 10.1016/j.bbrc.2019.05.011_bib25 article-title: Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype publication-title: J. Clin. Investig. doi: 10.1172/JCI99435 – volume: 13 start-page: 2048 year: 2015 ident: 10.1016/j.bbrc.2019.05.011_bib20 article-title: Ferritin-mediated iron sequestration stabilizes hypoxia-inducible factor-1alpha upon LPS activation in the presence of ample oxygen publication-title: Cell Rep. doi: 10.1016/j.celrep.2015.11.005 – volume: 453 start-page: 314 year: 2008 ident: 10.1016/j.bbrc.2019.05.011_bib23 article-title: Wound repair and regeneration publication-title: Nature doi: 10.1038/nature07039 – volume: 6 start-page: 827 year: 2016 ident: 10.1016/j.bbrc.2019.05.011_bib2 article-title: Lung structure and the intrinsic challenges of gas exchange publication-title: Comp. Physiol. doi: 10.1002/j.2040-4603.2016.tb00698.x – volume: 3 start-page: 349 year: 2002 ident: 10.1016/j.bbrc.2019.05.011_bib4 article-title: Myofibroblasts and mechano-regulation of connective tissue remodelling publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm809 – volume: 137 start-page: 1459 year: 2009 ident: 10.1016/j.bbrc.2019.05.011_bib12 article-title: Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice publication-title: Gastroenterology doi: 10.1053/j.gastro.2009.07.006 – volume: 48 start-page: 703 year: 2013 ident: 10.1016/j.bbrc.2019.05.011_bib24 article-title: Hedgehog signaling in neonatal and adult lung publication-title: Am. J. Respir. Cell Mol. Biol. doi: 10.1165/rcmb.2012-0347OC
SSID	ssj0011469
Score	2.3383892
Snippet	Pulmonary fibrosis is characterized by progressive and irreversible scarring of alveoli, which causes reduction of surface epithelial area and eventually...
SourceID	proquest pubmed crossref elsevier
SourceType	Aggregation Database Index Database Enrichment Source Publisher
StartPage	684
SubjectTerms	epithelium extracellular matrix Fibroblasts fibrosis GANT61 gene expression regulation Gli pathway lungs metabolism mice oncogenes Pulmonary fibrosis Scar signal transduction transcription (genetics) transcription factors translation (genetics) Wound healing
Title	Gli signaling pathway modulates fibroblast activation and facilitates scar formation in pulmonary fibrosis
URI	https://dx.doi.org/10.1016/j.bbrc.2019.05.011 https://www.ncbi.nlm.nih.gov/pubmed/31078262 https://www.proquest.com/docview/2231968436 https://www.proquest.com/docview/2286918057
Volume	514
WOSCitedRecordID	wos000470803000019&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVESC databaseName: Elsevier SD Freedom Collection Journals 2021 customDbUrl: eissn: 1090-2104 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0011469 issn: 0006-291X databaseCode: AIEXJ dateStart: 19950105 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1bb9MwFLa6DQQvCDYu5TIZCfFSBeUe-7FM4_YwIa2T-hbZjrOlK2nVJGP9lfwljuPY6UCrAImXKGqd1On3xeccnxtCbzxXEBJw1yFhLpwwY65DBbyPwg8lWANRIgRpm00kJydkOqVfB4MfJhfmap6UJbm-psv_CjV8BmCr1Nm_gNveFD6AcwAdjgA7HP8I-I_zYqSiMphONAcN7ztbq443qlGXrEY5GMgLDkpz3RbS0FuyrQ8hZ0LX7IZRlWCrPrOxjTVv5vAMKsiuvUNVVDccwoVqvdXXHuDFYmko0BUUUiHuG9koVpmfVM1l0wYVTFhdNWsrKM6k9kadsnpRXRR2M-iiUAGg7R4vnJ_LdXNZ9CspjAT6mW9LNXZza0NlU8XGS9Put5mcmxshoUrAOj5tG-2ABNPLtktdx-8aGZt1PdLZqR2Bg41VOtZd6TqBH-t-pb_JEr2tMXvH-UrVuvSoLvHq9ZLTxjOeqkmpOYE67BJY4nbQnp9EFJbZvfHn4-kX69gCwdRZZPohujwuHXL46y_dpivdZgu1OtHkIXrQGTN4rEn4CA1kuY8OxiXg9W2N3-I2vLj12-yju-_N2b0j02TwAM2ArdiyFXdsxZatuGcr7tmKgWF4g61YsRVbtuKixJat2LD1MTr7cDw5-uR07T8cEUZR7XhJxl3uM0m5CAOfBVJI4iZxkngiI0z6nMiME1BS89yTWRb5Scz8PJGEwZDYDZ6g3XJRymcIZzHngIzPPaYK83Mae3lAXMoDGoIEokPkmT86FV1tfNWiZZ6aIMhZqsBJFTipG6UAzhCN7DVLXRlm6-jI4Jd2uq3WWVOg29brXhuwU4BGefNYKRdNlYJeD9KThEG8bQyJqUfAJhuip5opdq5g14F1EPvP_3FmL9D9_p19iXbrVSNfoTviqi6q1SHaSabksGP_T2I28WA
linkProvider	Elsevier
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Gli+signaling+pathway+modulates+fibroblast+activation+and+facilitates+scar+formation+in+pulmonary+fibrosis&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.au=Tsukui%2C+Tatsuya&rft.au=Ueha%2C+Satoshi&rft.au=Shichino%2C+Shigeyuki&rft.au=Hashimoto%2C+Shinichi&rft.date=2019-06-30&rft.pub=Elsevier+Inc&rft.issn=0006-291X&rft.eissn=1090-2104&rft.volume=514&rft.issue=3&rft.spage=684&rft.epage=690&rft_id=info:doi/10.1016%2Fj.bbrc.2019.05.011&rft.externalDocID=S0006291X19308794
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0006-291X&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0006-291X&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0006-291X&client=summon