Expression And Value Of TPC2 Protein In Hepatic Stellate Cell Lysozyme

Background: Hepatic fibrosis is the early stage of cirrhosis.Chronic liver disease caused by various causes can induce hepatic fibrosis.China is a big country of chronic liver disease,the incidence of liver fibrosis is high from this point of view.At present,there is still no effective drug against liver fibrosis.A number of high-quality studies have shown that calcium channel blockers can inhibit liver fibrosis and even reverse early cirrhosis,But the exact mechanism is not yet clear.The aim of this study was to investigate the expression of lysosomal calcium channel protein TPC2 in hepatic stellate cells and its effect on HSC activation and collagen expression in hepatic stellate cell lysosomes.Methods:Western-blot was used to detect the expression of lysosome calcium channel protein(TPC2)and hepatic stellate cell activation marker a-SMA dealed with TGF ?1,PDGF and the NAADP-TPC2 pathway blocker Bafilomycin,while qRT-PCR detecting the expression of collagen I mRNA,and then confocal microscopy detecting the change of calcium signal under the action of liver fibrosis factor.Result: Expression of lysosome calcium channel protein TPC2 is down regulated after HSC is activated by TGF?1 or PDGF,while the expression of collagen I mRNA increased after HSC is activated by TGF?1 or PDGF,TPC 2 expression level was negatively correlated with collagen expression.Induced by TGF?1,PDGF,and Bafilomycin down-regulating expression of TPC2,while a-SMA expression increased,The expressions level of TPC 2 was negatively correlated.with a-SMA.Confocal microscope recording excitation signals at 380 nm and emission signals at 510 nm at 1-s intervals,under the stimulation of TGF?1,it showed a "double peak" change,suggesting that the "Two pool" effect of lysozyme calcium mobilization appeared under TGF?1 stimulation.Conclusions: TPC2 protein may participate in the pathogenesis of liver fibrosis.Hepatic fibrosis factors can activate liver stellate cells by down-regulating the expression of TPC2,induce collagen production,and then lead to the occurrence of liver fibrosis.TPC2 may be a potential regulatory target for liver fibrosis.