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 demonstrated that HRC was upregulated in fibrotic liver and activated HSCs. TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagens expression, and inhibited HSCs 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 while ER stress antagonist 4-phenylbutyric acid (4-PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate that depletion of HRC inhibited HSCs activation through ER stress pathway, and HRC may be a potential regulator of liver fibrosis.