title: Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells.
abstract: The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2+homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrates that HRC was upregulated in fibrotic liver and activated hepatic stellate cells (HSCs). TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagen expression, and inhibited HSC proliferation and migration. In addition, we found that the anti-fibrosis effect of HRC knockdown was associated with endoplasmic reticulum (ER) stress. Silencing of HRC decreased the expression of ER stress and autophagy markers. Moreover, ER stress agonist thapsigargin (TG) enhanced, whereas ER stress antagonist 4-phenylbutyric acid (4-PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate that depletion of HRC inhibited HSC activation through the ER stress pathway, and HRC may be a potential regulator of liver fibrosis.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.|Department of Gastroenterology, Zhoushan Hospital, Zhoushan 316000, China.
authors.forename: Mengke
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yunwu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China datian@tjh.tjmu.edu.cn liaojiazhi2011@163.com.
authors.forename: Dean
authors.identifier: http://orcid.org/0000-0002-1407-6351
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China datian@tjh.tjmu.edu.cn liaojiazhi2011@163.com.
authors.forename: Jiazhi
authors.initials: J
authors.lastname: Liao
keywords: ER stress; HRC; Hepatic stellate cells; Liver fibrosis