PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells

• Published in: Toxicology and applied pharmacology Vol. 292; pp. 8 - 18
• Main Authors: Chen, Pei-Jie, Cai, Shuang-Peng, Yang, Yang, Li, Wan-Xia, Huang, Cheng, Meng, Xiao-Ming, Li, Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2016
• Subjects: 60 APPLIED LIFE SCIENCES; ACTIN; Activation; ALANINES; AMINOTRANSFERASES; Animals; APOPTOSIS; Cell Line; CELL PROLIFERATION; Coculture Techniques; COLLAGEN; Dose-Response Relationship, Drug; FIBROSIS; GROWTH FACTORS; HEALING; Hepatic stellate cell (HSC); Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Inactivation; LIVER; Liver Cirrhosis - chemically induced; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver fibrosis; Male; Mice; MUSCLES; PHENOTYPE; Protein tyrosine phosphatase 1B (PTP1B); Protein Tyrosine Phosphatase, Non-Receptor Type 1 - biosynthesis; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - toxicity; Rats; RECEPTORS; TIME DEPENDENCE; TYROSINE; WOUNDS; PTPN1; PTPs; NAFLD; AST; aHSCs; ALT; Hepatic stellate cell (HSC); Activation; Liver fibrosis; Inactivation; iHSCs; ECM; col1α1; Protein tyrosine phosphatase 1B (PTP1B); α-SMA; PTP1B; MDI; qHSCs; TGF-β1; HSCs
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2015.12.021

Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was elevated in fibrotic liver but reduced after spontaneous recovery. Moreover, stimulation of HSC-T6 cells with transforming growth factor-β1 (TGF-β1) resulted in a dose/time-dependent increase of PTP1B mRNA and protein. Co-incubation of HSC-T6 cells with PTP1B-siRNA inhibited the cell proliferation and activation induced by TGF-β1. Additionally, both mRNA and protein of PTP1B were dramatically decreased in inactivated HSCs after treated with adipogenic differentiation mixture (MDI). Over-expression of PTP1B hindered the inactivation of HSC-T6 cells induced by MDI. These observations revealed a regulatory role of PTP1B in liver fibrosis and implied PTP1B as a potential therapeutic target. •The expression of PTP1B in the fibrotic livers and recovery livers•The expression of PTP1B in activated and inactivated HSCs•Blockade of PTP1B inhibited the TGF-β1-induced proliferation and activation of HSCs.•Over-expression of PTP1B abolished the inactivation of HSCs induced by MDI.