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Adipose-derived mesenchymal stem cells inhibit hepatic stellate cells activation to alleviate liver fibrosis via Hippo pathway

作者:Haifeng Liu, Haocheng Huang, Yifan Liu, Yuxue Yang, Hongchuan Deng, Xinmiao Wang, Ziyao Zhou, Guangneng Peng, Shouchao Jin, Dechun Chen, Zhijun Zhong · 发表于:Stem Cell Research & Therapy · 年份:2024 · DOI:10.1186/s13287-024-03988-7 · 被引用次数:10 · 研究领域:Hippo pathway signaling and YAP/TAZ、Liver physiology and pathology、Mesenchymal stem cell research

Liver fibrosis is a common pathological process of chronic liver disease, characterized by excessive deposition of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been found to have potential therapy effect on liver fibrosis, but the mechanism involved was still unclear. The objective of this study is to investigate the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADMSCs) on the treatment of liver fibrosis, with particular emphasis on elucidating the underlying mechanism of action through which ADMSCs inhibit the activation of hepatic stellate cells (HSCs). ADMSCs were isolated from adipose tissue and injected intravenously into hepatic fibrosis model of rats. The histopathological changes, liver function, collagen deposition, the expression of fibroin and Hippo pathway were evaluated. In vitro, ADMSCs were co-cultured with HSCs activated by transforming growth factor beta 1 (TGF-β 1 ), and the inhibitor of Hippo pathway was used to evaluate the therapeutic mechanism of ADMSCs transplantation. The results showed that after the transplantation of ADMSCs, the liver function of rats was improved, the degree of liver fibrosis and collagen deposition were reduced, and the Hippo signaling pathway was activated. In vitro, ADMSCs can effectively inhibit the proliferation and activation of HSCs induced by TGF-β 1 treatment. However, the inhibitory effect of ADMSCs was weakened after blocking the Hippo signaling pathway. ADMSCs inhibit HSCs activation ...