Hepatocyte growth factor inhibits tubular epithelial-myofibroblast transdifferentiation by suppression of angiotensin II via the JAK2/STAT3 signaling pathway

Tubular epithelial-myofibroblast transdifferentiation (TEMT) is important in the development of chronic renal failure. The present study investigated whether hepatocyte growth factor (HGF) inhibits TEMT, and whether this function may be associated with the inhibition of angiotensin II (AngII) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Human HK-2 kidney proximal tubular cells were divided into 4 groups and treated with AngII (1x10(-6) M), HGF (8x10(-3) M), AngII plus HGF or control conditions, followed by an assessment of apoptosis induction and the expression levels of alpha-smooth muscle actin (alpha-SMA), which is a marker of TEMT. as well as the activation level of JAK2, phosphorylated (p)-JAK2, STAT3 and p-STAT3 signaling pathways. In HK-2 cells, alpha-SMA mRNA and protein expression levels increased following treatment with AngII, however, decreased expression was observed following exposure to HGF. HGF counteracted the AngII-induced increase in the expression of alpha-SMA in HK-2 cells. Similar expression profiles were observed for the phosphorylated forms of JAK2 and STAT3, indicating the possible involvement of this signaling pathway. The results demonstrated that treatment of cells with AngII was associated with the induction of apoptosis when compared with the control. By contrast, treatment with HGF attenuated AngII-induced apoptosis. The results suggested that HGF may inhibit TEMT by inhibiting AngII through the JAK2/STAT3 signaling pathway in HK-2 cells and HGF may prevent apoptosis induced by AngII. The present study provides a basis for understanding the mechanisms involved in the inhibition of TEMT by HGF, which requires further investigation.