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Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis.

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Název: Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis.
Autoři: Chen, Peng, Zhou, Yi-kun, Han, Chun-shan, Chen, Liu-jing, Wang, Yi-ming, Zhuang, Zi-meng, Lin, Shuai, Zhou, Yan-heng, Jiang, Jiu-hui, Yang, Rui-li
Zdroj: Frontiers in Immunology; 5/12/2022, Vol. 13, p1-12, 12p
Témata: CIRRHOSIS of the liver, HUMAN stem cells, DECIDUOUS teeth, PYROPTOSIS, NLRP3 protein, REACTIVE oxygen species, SOFOSBUVIR
Abstrakt: Liver cirrhosis represents a type of end-stage liver disease with few effective therapies, which was characterized by damaged functional liver tissue due to long-term inflammation. Gasdermin D (GSDMD)-executed programmed necrosis is reported to be involved in inflammation. However, the role of GSDMD in liver cirrhosis remains unclear. In this study, we used a CCl4-induced cirrhosis model and found stem cells from human exfoliated deciduous teeth (SHED) infusion showed profound therapeutic effects for liver cirrhosis. Mechanistically, NLRP3 inflammasome-activated GSDMD and its pyroptosis were upregulated in liver cirrhosis, while SHED infusion could suppress the expression of GSDMD and Caspase-1, resulting in reduced hepatocyte pyroptosis and inflammatory cytokine IL-1β release. Consistently, SHED could inhibit the elevated expression of NLRP3, GSDMD and Caspase-1 induced by CCl4 treatment in vitro co-culture system, which was mediated by decreasing reactive oxygen species (ROS) generation. Moreover, the pyroptosis inhibitor disulfiram showed similar therapeutic effects for liver cirrhosis as SHED. In conclusion, SHED alleviates CCl4-induced liver cirrhosis via inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis. [ABSTRACT FROM AUTHOR]
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis.
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  Data: <searchLink fieldCode="AR" term="%22Chen%2C+Peng%22">Chen, Peng</searchLink><br /><searchLink fieldCode="AR" term="%22Zhou%2C+Yi-kun%22">Zhou, Yi-kun</searchLink><br /><searchLink fieldCode="AR" term="%22Han%2C+Chun-shan%22">Han, Chun-shan</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Liu-jing%22">Chen, Liu-jing</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Yi-ming%22">Wang, Yi-ming</searchLink><br /><searchLink fieldCode="AR" term="%22Zhuang%2C+Zi-meng%22">Zhuang, Zi-meng</searchLink><br /><searchLink fieldCode="AR" term="%22Lin%2C+Shuai%22">Lin, Shuai</searchLink><br /><searchLink fieldCode="AR" term="%22Zhou%2C+Yan-heng%22">Zhou, Yan-heng</searchLink><br /><searchLink fieldCode="AR" term="%22Jiang%2C+Jiu-hui%22">Jiang, Jiu-hui</searchLink><br /><searchLink fieldCode="AR" term="%22Yang%2C+Rui-li%22">Yang, Rui-li</searchLink>
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  Data: Frontiers in Immunology; 5/12/2022, Vol. 13, p1-12, 12p
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  Data: <searchLink fieldCode="DE" term="%22CIRRHOSIS+of+the+liver%22">CIRRHOSIS of the liver</searchLink><br /><searchLink fieldCode="DE" term="%22HUMAN+stem+cells%22">HUMAN stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22DECIDUOUS+teeth%22">DECIDUOUS teeth</searchLink><br /><searchLink fieldCode="DE" term="%22PYROPTOSIS%22">PYROPTOSIS</searchLink><br /><searchLink fieldCode="DE" term="%22NLRP3+protein%22">NLRP3 protein</searchLink><br /><searchLink fieldCode="DE" term="%22REACTIVE+oxygen+species%22">REACTIVE oxygen species</searchLink><br /><searchLink fieldCode="DE" term="%22SOFOSBUVIR%22">SOFOSBUVIR</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Liver cirrhosis represents a type of end-stage liver disease with few effective therapies, which was characterized by damaged functional liver tissue due to long-term inflammation. Gasdermin D (GSDMD)-executed programmed necrosis is reported to be involved in inflammation. However, the role of GSDMD in liver cirrhosis remains unclear. In this study, we used a CCl<subscript>4</subscript>-induced cirrhosis model and found stem cells from human exfoliated deciduous teeth (SHED) infusion showed profound therapeutic effects for liver cirrhosis. Mechanistically, NLRP3 inflammasome-activated GSDMD and its pyroptosis were upregulated in liver cirrhosis, while SHED infusion could suppress the expression of GSDMD and Caspase-1, resulting in reduced hepatocyte pyroptosis and inflammatory cytokine IL-1β release. Consistently, SHED could inhibit the elevated expression of NLRP3, GSDMD and Caspase-1 induced by CCl<subscript>4</subscript> treatment in vitro co-culture system, which was mediated by decreasing reactive oxygen species (ROS) generation. Moreover, the pyroptosis inhibitor disulfiram showed similar therapeutic effects for liver cirrhosis as SHED. In conclusion, SHED alleviates CCl<subscript>4</subscript>-induced liver cirrhosis via inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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        Value: 10.3389/fimmu.2022.860225
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        Text: English
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    Subjects:
      – SubjectFull: CIRRHOSIS of the liver
        Type: general
      – SubjectFull: HUMAN stem cells
        Type: general
      – SubjectFull: DECIDUOUS teeth
        Type: general
      – SubjectFull: PYROPTOSIS
        Type: general
      – SubjectFull: NLRP3 protein
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      – SubjectFull: REACTIVE oxygen species
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      – SubjectFull: SOFOSBUVIR
        Type: general
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      – TitleFull: Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis.
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              Text: 5/12/2022
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