文献类型：期刊文献

英文题名：MFAP2 promotes HSCs activation through FBN1/TGF-β/Smad3 pathway

作者：Sun, Yonghong[1,2];Chen, Xingxing[2];Chen, Lili[3];Bao, Baixin[3];Li, Chunming[4,6];Zhou, Yongning[1,5]

第一作者：Sun, Yonghong

通信作者：Zhou, YN[1];Li, CM[2]

机构：[1]Lanzhou Univ, Hosp 1, Dept Gastroenterol, Lanzhou, Peoples R China;[2]Gansu Prov Peoples Hosp, Dept Pediat, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Peoples R China;[4]Gansu Prov Peoples Hosp, Dept Obstet, Lanzhou, Peoples R China;[5]Lanzhou Univ, Hosp 1, Dept Gastroenterol, Lanzhou 730000, Gansu, Peoples R China;[6]Gansu Prov Peoples Hosp, Dept Obstet, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：Lanzhou Univ, Hosp 1, Dept Gastroenterol, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 1, Dept Gastroenterol, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Prov Peoples Hosp, Dept Obstet, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2023

卷号：27

期号：21

起止页码：3235

外文期刊名：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

收录：;Scopus(收录号：2-s2.0-85168909759);WOS:【SCI-EXPANDED(收录号:WOS:001063721700001)】；

基金：This research was funded by Science and Technology Project of Gansu Province (grant number 20JR10RA385, 18YF1WA040) and the Science Foundation of Gansu Province People's Hospital (grant no.19SYPYB-24, 18GSSY3-4).

语种：英文

外文关键词：FBN1; HSCs; liver fibrosis; MFAP2; TGF-beta 1

摘要：Liver fibrosis is a chronic inflammatory process characterized by the accumulation of extracellular matrix (ECM), which contributes to cirrhosis and hepatocellular carcinoma. Increasing evidence suggests that the activation of hepatic stellate cells (HSCs) under an inflammatory state leads to the secretion of collagens, which can cause cirrhosis. In this study, we analysed data from the Gene Expression Omnibus (GEO) databases to identify differentially expressed genes (DEGs) between quiescent and fibrotic HSCs. We found that Microfibril Associated Protein 2 (MFAP2) was elevated in carbon tetrachloride (CCl4)-induced liver fibrosis and Transforming Growth Factor-Beta 1 (TGF-beta 1)-activated HSCs. Knockdown of MFAP2 inhibited HSC proliferation and partially attenuated TGF-beta-stimulated fibrogenesis markers. Bioinformatics analysis revealed that Fibrillin-1 (FBN1) was correlated with MFAP2, and the expression of FBN1 was significantly upregulated after MFAP2 overexpression. Silencing MFAP2 partially attenuated the activation of HSCs by inhibiting HSC proliferation and decreasing collagen deposits. In vitro results showed that the inhibition of MFAP2 alleviated hepatic fibrosis by inhibiting the activation and inducing the apoptosis of active HSCs in a CCl4-induced mouse model. In conclusion, our results suggest that MFAP2 is a potential target for the clinical treatment of liver fibrosis.