Ubiquitin specific peptidase 1 promotes hepatic fibrosis through positive regulation of CXCL1 by deubiquitinating SNAIL

Du, Zhiyong1; Wu, Tianchong1; Liu, Linsen1; Luo, Biwei1; Wei, Cuifeng2

2022

10.1016/j.dld.2021.02.025

DIGESTIVE AND LIVER DISEASE   影响因子和分区

1590-8658

1878-3562

Background: Hepatic fibrosis is attributed to an imbalance of extracellular matrix production and lysis. Human hepatic stellate cells (HSCs) have been uncovered to converge through complex interactions with hepatocytes and immune cells, causing scarring in liver damage. Aims: We aimed to investigate the expression status of ubiquitin specific peptidase 1 (USP1) and its potential mechanisms on HSCs and hepatic fibrosis . Methods: Hepatic fibrosis animal and cell models were generated using mice with carbon tetrachloride (CCl4) treatment and HSCs LX-2 with TGF- beta 1 treatment. Relationships among USP1, SNAIL, and CXCL1 were identified via dual-luciferase reporter gene assay, co-immunoprecipitation, and chromatin immunoprecipitation. With gain- and loss-of-experiments, CCK-8 and flow cytometry assays were employed for cell proliferation and apoptosis. Results: USP1 upregulated SNAIL expression through deubiquitination to increase CXCL1 expression. USP1 downregulation decreased expressions of fibrosis-related genes, suppressed proliferation, and promoted apoptosis in TGF- beta 1-induced LX-2 cells, which were reversed by SNAIL overexpression. The profibrosis role caused by SNAIL upregulation was abolished by CXCL1 reduction. Promotive function of USP1/SNAIL/CXCL1 axis in hepatic fibrosis was further confirmed in vivo . Conclusion: These data supported siRNA-mediated silencing of USP1 improved hepatic fibrosis through inhibition of SNAIL and CXCL1, which yields a new therapeutic target for hepatic fibrosis treatment. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemokine (C-X-C motif) ligand 1 Deubiquitination Hepatic fibrosis Human hepatic stellate cell SNAIL Ubiquitin specific peptidase 1

SCI

英语

第一

National Natural Science Foundation of China[81470868] ; Cultivating Fund Project of Shenzhen People' s Hospital[201911] ; Science and Technology Innovation Foundation of Shenzhen[JCYJ20190807144807510] ; Shenzhen Healthcare Research Project[SZFZ2017080]

Gastroenterology & Hepatology

Gastroenterology & Hepatology

WOS:000737016100013

ELSEVIER SCIENCE INC

CLINICAL MEDICINE

Web of Science

1.Southern Univ Sci & Technol, Dept Hepatobiliary & Pancreat Surg, Shenzhen Peoples Hosp, Clin Med Coll 2,Jinan Univ,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
2.Jingmen First Peoples Hosp, Dept Endocrinol, Jingmen 448000, Peoples R China

Du, Zhiyong,Wu, Tianchong,Liu, Linsen,et al. Ubiquitin specific peptidase 1 promotes hepatic fibrosis through positive regulation of CXCL1 by deubiquitinating SNAIL[J]. DIGESTIVE AND LIVER DISEASE,2022,54(1).

Du, Zhiyong,Wu, Tianchong,Liu, Linsen,Luo, Biwei,&Wei, Cuifeng.(2022).Ubiquitin specific peptidase 1 promotes hepatic fibrosis through positive regulation of CXCL1 by deubiquitinating SNAIL.DIGESTIVE AND LIVER DISEASE,54(1).

Du, Zhiyong,et al."Ubiquitin specific peptidase 1 promotes hepatic fibrosis through positive regulation of CXCL1 by deubiquitinating SNAIL".DIGESTIVE AND LIVER DISEASE 54.1(2022).