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Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells

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单位: [1]Huazhong Univ Sci & Technol, Dept Gastroenterol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China [2]Zhoushan Hosp, Dept Gastroenterol, Zhoushan 316000, Peoples R China
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关键词: Liver fibrosis Hepatic stellate cells HRC ER stress

摘要:
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-beta treatment increased alpha-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced alpha-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.

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 3 区 生物学
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 生物学
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出版当年[2015]版:
Q2 BIOLOGY
最新[2023]版:
Q3 BIOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Dept Gastroenterol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China
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