Frontiers in Immunology (May 2022)
Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis
- Peng Chen,
- Peng Chen,
- Peng Chen,
- Yi-kun Zhou,
- Yi-kun Zhou,
- Yi-kun Zhou,
- Chun-shan Han,
- Chun-shan Han,
- Chun-shan Han,
- Liu-jing Chen,
- Liu-jing Chen,
- Liu-jing Chen,
- Yi-ming Wang,
- Yi-ming Wang,
- Yi-ming Wang,
- Zi-meng Zhuang,
- Zi-meng Zhuang,
- Zi-meng Zhuang,
- Shuai Lin,
- Shuai Lin,
- Shuai Lin,
- Yan-heng Zhou,
- Yan-heng Zhou,
- Yan-heng Zhou,
- Jiu-hui Jiang,
- Jiu-hui Jiang,
- Jiu-hui Jiang,
- Rui-li Yang,
- Rui-li Yang,
- Rui-li Yang
Affiliations
- Peng Chen
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Peng Chen
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Peng Chen
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Yi-kun Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Yi-kun Zhou
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Yi-kun Zhou
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Chun-shan Han
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Chun-shan Han
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Chun-shan Han
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Liu-jing Chen
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Liu-jing Chen
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Liu-jing Chen
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Yi-ming Wang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Yi-ming Wang
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Yi-ming Wang
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Zi-meng Zhuang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Zi-meng Zhuang
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Zi-meng Zhuang
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Shuai Lin
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Shuai Lin
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Shuai Lin
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Yan-heng Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Yan-heng Zhou
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Yan-heng Zhou
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Jiu-hui Jiang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Jiu-hui Jiang
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Jiu-hui Jiang
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- Rui-li Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China
- Rui-li Yang
- National Clinical Research Center for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
- Rui-li Yang
- Beijing Key Laboratory of Digital Stomatology, Beijing, China
- DOI
- https://doi.org/10.3389/fimmu.2022.860225
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
