-Original-

Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Jie Fu, Huihui Du, Xiao Zhang and Xundi Xu

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, 2001 of Jingwei Building, The Second Xiangya Hospital, Central South University, Hunan, China

Background: Transient receptor potential vanilloid 4 (TRPV4) is a member of the TRP channel family and is involved in diverse physiological and pathological processes. Accumulating evidence from in vitro studies indicates that TRPV4 has a potential role in liver fibrosis, but its precise role in the pathophysiological development of this condition is unclear. Exogenous interventions and endogenous reactions should be considered.
Methods: This study used a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis to investigate the effects of intraperitoneal injection of the novel TRPV4 channel selective agonist GSK1016790A (GSK) and antagonist HC-067047 (HC).
Results: As compared with the CCl4 group, collagen fiber deposition and alpha-smooth muscle actin (α-SMA) levels were markedly higher and hepatic lobule disorganization was worse in the CCl4+GSK group, while collagen fiber deposition was significantly lower and hepatic lobule disorganization was less severe in the CCl4+HC group.
Conclusions: The present findings suggest that activation of TRPV4 channels worsens liver fibrosis and that inhibition of TRPV4 channels may alleviate liver fibrosis in vivo.

J Nippon Med Sch 2019; 86: 258-262

Keywords
TRPV4, liver fibrosis, in vivo

Correspondence to
Xundi Xu, Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, 2001 of Jingwei Building, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
xuxundi@csu.edu.cn

Received, December 12, 2018
Accepted, April 17, 2019