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

• Published in: Frontiers in immunology 2022-05, Vol.13, p.860225-860225
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Caspase 1 - metabolism; GSDMD; Hepatocytes - metabolism; Humans; Immunology; Inflammation; Intracellular Signaling Peptides and Proteins - metabolism; liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - therapy; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Phosphate-Binding Proteins - metabolism; Pyroptosis; Stem Cells - metabolism; stem cells from human exfoliated deciduous teeth; Tooth, Deciduous
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.860225

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 -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 treatment 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 -induced liver cirrhosis inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis.