Dexmedetomidine alleviates high glucose-induced podocyte damage by inhibiting EDA2R

Abstract

Purpose: To investigate the effect and mechanism of action of dexmedetomidine (Dex) on podocyte injury.
 Methods: Cells were incubated with high glucose (50 mM) to induce a podocyte injury model in vitro. Cell viability, apoptosis, the expression of related protein related in podocyte injury and albumin permeability were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), flow cytometry, western blot and Transwell assays.
 Results: Dex administration enhanced HG-induced cell viability and the relative protein expression of Bcl-2, but reduced the HG-induced relative protein level of Bax and apoptosisrate in podocytes (p < 0.05). Besides, Dex incubation compensated HG-induced relative protein expressions of nephrin and podocin in podocytes but did the reverse with regard to relative protein expression of desmin and albumin permeability (p < 0.05). Moreover, Dex treatment resulted in a decrease in ectodysplasin A2 receptor (EDA2R) expression in HG-induced podocytes. The level of EDA2R was upregulated by the transfection of overexpression plasmid containing the EDA2R sequences. Overexpression of EDA2R reversed Dex-induced increase in cell viability, apoptosis, expression of nephrin, podocin and desmin, as well as albumin permeability in HG-stimulated podocytes (p < 0.05).
 Conclusion: Dex ameliorates HG-induced podocyte injury via inhibition of EDA2R, indicating that Dex is a potential alternative drug for the treatment of podocyte injury.