MFAP2 promotes HSCs activation through FBN1/TGF-β/Smad3 pathway.

Autor: Sun Y; Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.; Department of Pediatrics, Gansu Province People's Hospital, Lanzhou, People's Republic of China., Chen X; Department of Pediatrics, Gansu Province People's Hospital, Lanzhou, People's Republic of China., Chen L; The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, People's Republic of China., Bao B; The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, People's Republic of China., Li C; Department of Obstetrics, Gansu Province People's Hospital, Lanzhou, People's Republic of China., Zhou Y; Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2023 Nov; Vol. 27 (21), pp. 3235-3246. Date of Electronic Publication: 2023 Aug 27.
DOI: 10.1111/jcmm.17884
Abstrakt: 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-β1)-activated HSCs. Knockdown of MFAP2 inhibited HSC proliferation and partially attenuated TGF-β-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.
(© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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