KLF11 enhances the effect of liraglutide in high glucose-induced Schwann cells by regulating endoplasmic reticulum stress and autophagy through inactivation of P38 MAPK

Purpose: To investigate the effect of Kruppel-Like Factor 11 (KLF11) on diabetic peripheral neuropathyMethods: Schwann cells, RSC96, were treated with high glucose to induce DPN. Cell viability and apoptosis were evaluated by flow cytometry. Expressions of KLF11 and proteins involved in endoplasmic reticulum (ER) stress and autophagy were evaluated by western blot.Results: The KLF11 was downregulated in high glucose-induced RSC96. Cell viability of RSC96 was decreased and apoptosis increased by high glucose. Overexpression of KLF11 restored viability and decreased apoptosis of high glucose-induced RSC96. High glucose-induced an increase in proteins involved in ER stress in RSC96, and but reversed by KLF11 overexpression. Overexpression of KLF11 also attenuated high glucose-induced decrease in LC3 and Beclin1 expression in RSC96 cells. Phosphorylated p38 (p-p38) in high glucose-induced RSC96 decreased upon overexpression of KLF11. Liraglutide treatment increased cell viability and autophagy, decreased cell apoptosis, and inhibited ER stress in high glucose-induced RSC96. Furthermore, KLF11 enhanced the protective activity of liraglutide against high glucose-induced cytotoxicity in Schwann cells.Conclusion: Overexpression of KLF11 exerts a neuroprotective effect against DPN by promoting autophagy and inhibiting ER stress via inactivation of p38 signaling, suggesting that KLF11 might be a target for DPN.