Knockdown of ALK7 inhibits high glucose‐induced oxidative stress and apoptosis in retinal pigment epithelial cells

Abstract Diabetic retinopathy (DR) is one of the diabetic complications associated with hyperglycaemia‐mediated oxidative stress. Activin receptor‐like kinase 7 (ALK7) has been proven to be a potential therapeutic approach for diabetic cardiomyopathy, which is another diabetic complication. However, the role of ALK7 in DR remains unclear. In the current study, ALK7 was found to be up‐regulated in clinical samples from DR patients and high glucose (HG)‐induced human retinal pigment epithelial cells (ARPE‐19). In vitro studies demonstrated that knockdown of ALK7 in ARPE‐19 cells through transfection with siRNA‐ALK7 (si‐ALK7) improved cell viability in HG‐induced ARPE‐19 cells. Knockdown of ALK7 suppressed HG‐induced reactive oxygen species (ROS) production, as well elevating the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in ARPE‐19 cells. The number of apoptotic cells was significantly decreased after transfection with si‐ALK7. ALK7 knockdown also caused a significant decrease in bax expression and an increase in bcl‐2 expression in HG‐induced ARPE‐19 cells. In addition, ALK7 knockdown resulted in remarkable increase in the expressions of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase‐1 (HO‐1) in ARPE‐19 cells in response to HG induction. Taken together, knockdown of ALK7 protected ARPE‐19 cells from HG‐induced oxidative injury, which might be mediated by the activation of the Nrf2/HO‐1 signalling pathway.