HAS2受TGF-β1/MeCP2轴作用促进慢性胰腺炎中胰腺星状细胞的活化

he pathogenesis of chronic pancreatitis (CP) remains unclear. Few studies have investigated the role of hyaluronic acid synthetase 2 (HAS2) in CP tissue and its effects on pancreatic stellate cells (PSCs). The purpose of this study was to investigate the effect of HAS2 on the occurrence and development of CP fibrosis through the activation of PSCs. Firstly, the effects of up-regulation and down-regulation of HAS2 on α-smooth muscle actin (α-SMA) expression in PSCs were investigated by RT-qPCR and Western blotting. Secondly, the regulatory effects of HAS2 on the fibroblast phenotype of PSCs were investigated by cell wound healing assay, transwell assay and CCK-8 assay. Then, the rescue assay was used to investigate whether HAS2 was regulated by the TGF-β1/MeCP2 axis. Finally, the CP rat model was constructed to explore whether the expression of HAS2 and MeCP2 was increased, and Pearson linear correlation was used to investigate the correlation between the expression level of HAS2 and the degree of pancreatic fibrosis. The results revealed that HAS2 promoted α-SMA expression in PSCs, and the down-regulation of HAS2 inhibited the migration and proliferation of PSCs. Knockdown of HAS2 in PSCs inhibits MeCP2-induced α-SMA expression and HAS2 is regulated by TGF-β1/MeCP2 axis. The expressions of HAS2 and MeCP2 were increased in CP model rats compared with the control group, and the expression levels of HAS2 were positively correlated with degree of pancreatic fibrosis. In conclusion, HAS2 can induce PSCs to activate and maintain the fibrotic phenotype of PSCs, and this effect is regulated by TGF-β1/MeCP2 axis.