PM2.5-exposed hepatocytes induce hepatic stellate cells activation by releasing TGF-ß1.

ABSTRACT

The interaction between various types of hepatic cells is related to liver fibrosis. Recent studies demonstrated that fine particulate matter (PM2.5) exposure is an important risk factor for the occurrence of liver fibrosis, but its molecular mechanism is still obscure. In this study, we aimed to investigate whether transforming growth factor- ß1 (TGF- ß1) secreted from PM2.5-treated hepatocytes (L-O2) are shuttled to hepatic stellate cells (HSCs) and to establish their effects on HSCs. We have observed that the conditioned medium from L-O2 cells stimulated with PM2.5 induced the activation of LX-2 cells, and at the same time, the same results were obtained when we co-cultured LX-2 in PM2.5-exposed L-O2 cells. In addition, analysis of L-O2 cells stimulated with PM2.5 revealed significant increases in TGF-ß1 expression. Moreover, we found that the TGF-ß1 receptor inhibitor, SB-525334, decreases the proliferation and migration of LX-2 cells in the co-culture system. In addition, the expression of α-smooth muscle actin and type I collagen in LX-2 cells induced by PM2.5-treated L-O2 cells were also blocked by pretreated with SB-525334. These observations imply that PM2.5 induces TGF- ß1expression in hepatocytes, which leads to HSCs activation.