title: PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells.
abstract: 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.
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Pei-Jie
authors.initials: PJ
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Shuang-Peng
authors.initials: SP
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Wan-Xia
authors.initials: WX
authors.lastname: Li
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University (ILD-AMU), Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis* / Q000633:toxicity*; D051381:Rats
chemical_list: D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse
keywords: Activation; Hepatic stellate cell (HSC); Inactivation; Liver fibrosis; Protein tyrosine phosphatase 1B (PTP1B)