TAK1 as the mediator in the protective effect of propofol on renal interstitial fibrosis induced by ischemia/reperfusion injury.

Ischemia-reperfusion injury (IRI), which is a major cause of acute and chronic renal dysfunction, induces both apoptosis and fibrotic processes. The mitogen-activated protein kinase kinase kinase transforming growth factor-β-activated kinase 1 (TAK1) was implicated in the processes of inflammation and fibrosis. The protective effect of propofol on renal functionality after acute kidney injury (AKI) in mice has been identified, whereas the mechanisms underlying fibrosis induced by kidney injury remain obscure. Herein, we investigated whether the protective effect of propofol on renal interstitial fibrosis induced by ischemia/reperfusion injury was modulated by TAK1 in renal ischemia /reperfusion (I/R) mouse models. The results of immunohistochemistry and western blotting revealed that TAK1 was significantly upregulated in IR group versus the control group, which was reversed by propofol administration. In addition, fibronectin (FN), α-smooth muscle actin (α-SMA) and type I collagen (COL1) were significantly downregulated and Tunnel staining revealed the number of tubular apoptotic cells was markedly reduced in IRP group versus IR group. Collectively, our results validated that propofol could ameliorate the IRI-induced renal interstitial fibrosis in mice by downregulation of TAK1 and inhibition of apoptosis at the early stage.