TRPM8 deficiency attenuates liver fibrosis through S100A9-HNF4α signaling.

ECM HNF4α Inflammation Liver fibrosis S100A9 TRPM8

Journal

Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195

Informations de publication

Date de publication:
07 May 2022
Historique:
received: 26 12 2021
accepted: 18 04 2022
entrez: 7 5 2022
pubmed: 8 5 2022
medline: 8 5 2022
Statut: epublish

Résumé

Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis. The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8 Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis.

Sections du résumé

BACKGROUND BACKGROUND
Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis.
METHODS METHODS
The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8
RESULTS RESULTS
Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl
CONCLUSIONS CONCLUSIONS
These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis.

Identifiants

DOI: 10.1186/s13578-022-00789-4 PMID: 35525986 PMC: PMC9080211
pubmed: 35525986
doi: 10.1186/s13578-022-00789-4
pii: 10.1186/s13578-022-00789-4
pmc: PMC9080211
doi:

Types de publication

Journal Article

Langues

eng

Pagination

58

Subventions

Organisme : National Natural Science Foundation of China
ID : 81670111
Organisme : Hunan Provincial Key Research and Development Program
ID : 2019SK2242

Informations de copyright

© 2022. The Author(s).

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Auteurs

Qiang Liu (Q)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.
Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China.

Xiaohua Lei (X)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Zhenyu Cao (Z)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Ju Zhang (J)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Likun Yan (L)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Jie Fu (J)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Qing Tong (Q)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Wei Qin (W)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Yaoli Shao (Y)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Chun Liu (C)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Zhiqiang Liu (Z)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Zicheng Wang (Z)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Yuan Chu (Y)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Ge Xu (G)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Siyuan Liu (S)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Xueyi Wen (X)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China.

Hirofumi Yamamoto (H)

Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita City, Osaka, 565-0871, Japan.

Masaki Mori (M)

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.

Xin M Liang (XM)

Wellman Center for Photomedicine, Division of Hematology and Oncology, Division of Endocrinology, Massachusetts General Hospital, VA Boston Healthcare System, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA. xin.m.liang.phd@gmail.com.

Xundi Xu (X)

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, 139 Renminzhong Road, Changsha, 410011, People's Republic of China. xuxundi@csu.edu.cn.
Department of General Surgery, Health Science Center, South China Hospital, Shenzhen University, No.1, Fuxin Road, Pinghu Street, Longgang District, Shenzhen, 518116, People's Republic of China. xuxundi@csu.edu.cn.

Classifications MeSH