Inhibition of the transient receptor potential vanilloid 3 channel attenuates carbon tetrachloride-induced hepatic fibrosis

被引：9

作者：

Yan, Likun ^{[1
]}

Zhang, Xiao ^{[1
]}

Fu, Jie ^{[1
]}

Liu, Qiang ^{[1
]}

Lei, Xiaohua ^{[1
]}

Cao, Zhenyu ^{[1
]}

Zhang, Ju ^{[1
]}

Shao, Yaoli ^{[1
]}

Tong, Qing ^{[1
]}

Qin, Wei ^{[1
]}

Liu, Xinxu ^{[1
]}

Liu, Chun ^{[1
]}

Liu, Zhiqiang ^{[1
]}

Li, Zhenghao ^{[1
]}

Lu, Jueliang ^{[1
]}

Xu, Xundi ^{[1
,2
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Hunan Prov Key Lab Hepatobiliary Dis Res, Changsha 410011, Hunan, Peoples R China

[2] Shenzhen Univ, Dept Gen Surg, Hlth Sci Ctr, Pinghu Hosp, Shenzhen 518116, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2021年 / 558卷

基金：

中国国家自然科学基金;

关键词：

TRPV3; Liver fibrosis; Inflammation; siRNA; RNA sequencing; LOX-1; STELLATE CELLS; ACTIVATION; EXPRESSION; APOPTOSIS; TRPV3; INFLAMMATION; LOX-1;

D O I：

10.1016/j.bbrc.2021.04.065

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl4-induced hepatic fibrosis mouse model. The TRPV3 selective agonist drofenine and its inhibitor, forsythoside B, were intraperitoneally injected to investigate the relationship between TRPV3 and liver fibrosis progression. Finally, in vitro studies were performed using hepatic stellate cells (HSCs) to discover the potential molecular biological mechanisms. Immunohistochemistry revealed TRPV3 overexpression in liver cirrhosis. In the liver fibrosis groups, TRPV3 inhibitor treatment significantly reduced liver fibrosis, while TRPV3 agonist exacerbated its progression. In HSCs, knocking down TRPV3 with siRNA impaired DNA synthesis and cell proliferation and increased cell apoptosis. Furthermore, we found that knockdown of TRPV3 could reduce the lectin like oxidized lowdensity lipoprotein receptor-1 (LOX-1) protein levels. Our research suggests that lower expression or functional levels of TRPV3 can ameliorate the inflammatory response and fibrotic tissue proliferation. (C) 2021 Elsevier Inc. All rights reserved.

引用

页码：86 / 93

页数：8

共 38 条

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