Glycogen Synthase Kinase 3β/β-Catenin Signaling but Not Hypoxia-Inducible Factor-1α Contributes to Defective Renal Wound Healing during Hypoxia

During wound healing, hypoxia, partly as a result of vascular damage and decreased blood supply along with increased oxygen consumption of wounded cells, induces angiogenesis and tissue remodeling but may also affect the healing response of parenchymal cells. Peng et al. investigated whether and how hypoxia affects wound healing in parenchymal cells in injured organs, such as the kidneys. When renal proximal tubular cells (RPTC) are exposed to hypoxic conditions (1% oxygen), wound healing (scratch model) and migration are significantly slower. Hypoxia-inducible factor-1α (HIF-1α) was induced by wounding under normoxic and enhanced under hypoxic conditions; however, scratch-wound healing was not significantly affected by either pharmacological activation of HIF or genetic deletion of HIF-1. The induction of β-catenin during hypoxia is accompanied by glycogen synthase kinase 3β (GSK3β) inactivation (possibly by Akt activation) and can be mimicked by pharmacological inhibition of GSK3β. Significantly higher Akt activation was observed during wound healing under hypoxia. These results suggest that hyperactivation of Akt by wound healing in hypoxic cells may inactivate GSK3β, resulting in the induction of β-catenin to prevent wound healing in renal tubular cells under hypoxia.

See article at J Pharmacol Exp Ther 2012, 340:176–184