ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway

Abstract

Objective. Activin receptor-like kinase 7 (ALK7) is a member of the ALK family that has a key role in diabetes. However, the role of ALK7 in diabetic nephropathy (DN) remains unclear. Methods. Herein, we evaluated the effects of ALK7 on mesangial cells (MCs). MCs were transfected with si-ALK7 or pcDNA3.0-ALK7, and then stimulated with 40 mM glucose for 24 h. Cell proliferation was detected by MTT assay. Relative ROS level was detected using DCFH-DA staining. The contents of inflammatory cytokines were determined by ELISA. Western blot analysis was used to determine the expression levels of FN, Col IV, Nrf2, and HO-1 in MCs. Results. Our results showed that ALK7 expression was induced by HG in MCs. Knockdown of ALK7 inhibited HG-induced cell proliferation. The HG-induced ROS was mitigated by si-ALK7 with decreased ROS level and NOX activity. In addition, ALK7 knockdown exhibited anti-inflammatory activity in HG-stimulated MCs. Moreover, ALK7 knockdown attenuated fibronectin (FN) and collagen IV (Col IV) expression in MCs. Knockdown of ALK7 enhanced Nrf2/HO-1 pathway in MCs. Inhibition of Nrf2 reversed the protective effects of ALK7 knockdown on HG-stimulated MCs. Conclusion. ALK7 knockdown exerted protective effects on HG-stimulated MCs through activation of the Nrf2/HO-1 pathway. Thus, targeting ALK7 might be a therapeutic approach for the treatment of DN.