Role Of HRC On Hepatic Stellate Cell Activationand Liver Fibrosis

Aim: The calcium-binding protein HRC is believed to regulate cell growth and migration of liver cancer. Herein, we aimed to determine whether HRC mediates the pathogenesis of liver fibrosis.Methods: The distribution and expression HRC in liver cirrhotic patients and TAA-induced fibrosis rats were detected by immunohistochemistry, quantitative reverse transcription polymerase chain reaction(RT-PCR) and western blot assay. Rat primary HSC were cultured, and activated spontaneouslyor stimulated with transforming growth factor(TGF)-?. LX-2 cells were transfected with HRC si RNA to downregluate expression of HRC. LX-2 cells were treated with ER stress agonist or antagonist. The levels of HRC, ?-smooth muscle actin(SMA), collagen type I, collagen type I, CTGF, endoplasmic reticulum(ER)stress key molecules, such as C/EBP homologous protein(CHOP), glucose-regulated protein 78(GRP78), activating transcription factor(ATF)4were detected by RT-PCR and western blot.Results: Liver cirrhotic patients and TAA-induced fibrosis rats showed a much higher level of HRC compared with the controls. HRC expression and ER stress could be induced during the process of cultured HSC activation. TGF-?1 treatment increased HRC expression dose-dependently in primary HSC and LX-2 cells. Knockdown of HRC in LX-2 cells reduced the activation, proliferation and migration of HSC. Moreover, the levels of ER stress markers were obviously decreased in HRC-knpckdown LX-2 cells. ER stress agonist enhanced HSC activation, and however, ER stress antagonist alleviated HSC activation.Conclusion: HRC silence could inhibit HSC activation, proliferation and migration, in which ER stress may be the underlying mechanisms. HRC may be an effective indicator for liver cirrhosis.