PIAS1 alleviates diabetic peripheral neuropathy through SUMOlation of PPAR-γ and miR-124-induced downregulation of EZH2/STAT3.

ABSTRACT: Diabetic peripheral neuropathy (DPN) is a frequently occurring chronic complication of diabetes. In this study, we aim to explore the regulatory mechanism of protein inhibitor of activated STAT1 (PIAS1) in DPN in terms of autophagy and apoptosis of Schwann cells. The SUMOlation of PPAR-γ by PIAS1 was examined, and ChIP was performed to verify the binding of PPAR-γ to miR-124 promoter region. Dual-luciferase gene reporter assay was used to validate the binding affinity between miR-124 and EZH2/STAT3. Following loss- and gain-of-function experiments, in vitro assays in high glucose-treated Schwann cells (SC4) and in vivo assays in db/db and ob/ob mice were performed to detect the effects of PIAS1 on autophagy and apoptosis of Schwann cells as well as symptoms of DPN by regulating the PPAR-γ-

SUBMITTER: Hou Z 

PROVIDER: S-EPMC8639830 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature