BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway

Hanjing Zhangdi; Xinyu Geng; Ning Li; Ruiling Xu; Ying Hu; Jingyang Liu; Xu Zhang; Jihan Qi; Yingying Tian; Jiawei Qiu; Shiling Huang; Xueyu Cang; Shizhu Jin

doi:10.1016/j.heliyon.2023.e21010

BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway

Heliyon. 2023 Oct 20;9(11):e21010. doi: 10.1016/j.heliyon.2023.e21010. eCollection 2023 Nov.

Authors

Hanjing Zhangdi^{1

2}, Xinyu Geng¹, Ning Li¹, Ruiling Xu¹, Ying Hu¹, Jingyang Liu¹, Xu Zhang¹, Jihan Qi¹, Yingying Tian¹, Jiawei Qiu¹, Shiling Huang¹, Xueyu Cang¹, Shizhu Jin¹

Affiliations

¹ Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
² Future Medical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Abstract

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the β-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and β-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/β-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/β-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.

Keywords: BMSCs; Fstl1; Liver cirrhosis; Wnt/β-Catenin.