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

Clin Exp Pharmacol Physiol. 2020 Feb;47(2):313-321. doi: 10.1111/1440-1681.13189. Epub 2019 Nov 19.


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.

Keywords: Nrf2/HO-1 signalling pathway; activin receptor-like kinase 7; diabetic retinopathy; high glucose; oxidative stress.

MeSH terms

  • Activin Receptors, Type I / deficiency*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Line
  • Cell Survival
  • Gene Knockdown Techniques / methods
  • Glucose / toxicity*
  • Humans
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism*


  • Reactive Oxygen Species
  • ACVR1C protein, human
  • Activin Receptors, Type I
  • Glucose