IRE1? siRNA relieves endoplasmic reticulum stress-induced apoptosis and alleviates diabetic peripheral neuropathy in vivo and in vitro.

ABSTRACT: Diabetic peripheral neuropathy (DPN) is mainly characterized by demyelination resulted from the apoptosis of the Schwann cell (SCs). Although the exact mechanisms underlying DPN remain unclear, endoplasmic reticulum (ER) stress is strongly implicated in the apoptosis. Under ER stress, activated inositol-requiring kinase 1? (IRE1?) unregulated CHOP, phosphorylated JNK and Caspase-12 to aggravate apoptosis-mediated damage of DPN. Therefore, we tested the hypothesis that inhibition of IRE1? could reduce the ER stress-related apoptosis to relieve DPN. Here, we show that IRE1? siRNA improved the neurological morphology and function of DPN rats and rescued ER stress-related apoptosis in the sciatic nerve. Additionally, RSC96 cells transfected with IRE1? siRNA were used as in vitro model of DPN. It was found that IRE1? siRNA also decreased high glucose-induced apoptosis and inhibited ER stress-related apoptosis in the cells. Altogether, our results suggest that IRE1? should be considered a potential therapeutic agent for DPN.

SUBMITTER: Yao W 

PROVIDER: S-EPMC5803253 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature