Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice.
Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice.
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DOI：
10.1272/jnms.jnms.2019_86-407
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发表时间：
2019-10
期刊：
影响因子：
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通讯作者：
Jie Fu;Huihui Du;Xiao Zhang;Xundi Xu
中科院分区：
文献类型：
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作者：
Jie Fu;Huihui Du;Xiao Zhang;Xundi Xu
背景技术瞬时受体电位香草酸4(TRPV4)是TRP通道家族的成员，参与多种生理和病理过程。越来越多的体外研究证据表明 TRPV4 在肝纤维化中具有潜在作用，但其在肝纤维化病理生理发展中的确切作用尚不清楚。应考虑外源干预和内源反应。方法本研究采用四氯化碳（CCl4）诱导的肝纤维化小鼠模型，研究腹腔注射新型TRPV4通道选择性激动剂GSK1016790A（GSK）和拮抗剂HC-067047（HC）的效果。结果 与CCl4组相比，CCl4+GSK组胶原纤维沉积和α-平滑肌肌动蛋白（α-SMA）水平明显升高，肝小叶紊乱更严重；而CCl4+HC组胶原纤维沉积明显减少，肝小叶紊乱更轻。结论 目前的研究结果表明，TRPV4 通道的激活会恶化肝纤维化，而抑制 TRPV4 通道可能会减轻体内肝纤维化。
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.