TRPM8 deficiency attenuates liver fibrosis through S100A9-HNF4α signaling.

Cell Biosci

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.

Published: May 2022

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: The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8 (KO) fibrotic mice after carbon tetrachloride (CCl) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments.

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- and BDL- treated TRPM8 mice. A strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells that underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, the alleviative effect of a selective TRPM8 antagonist was confirmed in vivo.

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080211PMC
http://dx.doi.org/10.1186/s13578-022-00789-4DOI Listing

Publication Analysis

Top Keywords

liver fibrosis
20
trpm8 deficiency
12
trpm8
11
fibrosis s100a9-hnf4α
8
s100a9-hnf4α signaling
8
evaluated specimens
8
fibrotic mice
8
liver
7
fibrosis
7
deficiency attenuates
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!