Grape seed proanthocyanidin extract attenuates high glucose-induced epithelial-mesenchymal transition of podocytes and alleviates streptozotocin diabetic renal injury

BACKGROUND Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus.Podocyte epithelial-mesenchymal transition (EMT) can induce podocyte injury and participate in the progression of DN.Grape seed proanthocyanidin extract (GSPE) possesses antioxidant and organ-protective effects.Nevertheless, whether GSPE suppresses podocyte EMT and ameliorates renal injury in DN remains poorly defined.AIM To investigate whether GSPE inhibits podocyte EMT and relieves renal injury in DN.METHODS Human podocytes were randomly divided into three groups and cultured for 72 hours: Control, high glucose (HG), and HG plus GSPE intervention groups.Cellular morphological changes, viability, and migration associated with EMT were observed.Western blotting and immunofluorescence detected expression of EMT-related markers and transforming growth factor (TGF)-β1/Smad signaling proteins.Eighteen Sprague-Dawley rats were assigned into three groups of six: Normal control, DN model, and GSPE-treated DN groups.After 8 weeks of intervention, 24-hour urinary protein (24-h UP), serum biochemical parameters, and oxidative stress indicators were measured.The renal expression of nephrin and synaptopodin was further detected to evaluate the protective effect of GSPE on DN.RESULTS HG induced the morphological transformation of human podocytes from an epitheliallike to a fibroblast-like phenotype.GSPE partially reversed these morphological changes and restored the cobblestone-like phenotype of podocytes.Compared with the Zheng ZF, Jiang L. Grape seed proanthocyanidin extract attenuates high glucoseinduced epithelial-mesenchymal transition of podocytes and alleviates streptozotocin diabetic renal injury.World J Diabetes 2026; In press