MicroRNA‐7a‐5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c‐JUN pathway

Abstract

Aims:The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA-7a-5p (miR-7a-5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR-7a-5p in DPN. Methods: DPN cell model was constructed with high-glucose-induced RSC96 cells. Cell apoptosis and viability were detected by flow cytometry analysis and cell counting kit-8 (CCK-8) assay respectively. The apoptosis and Jun N-terminal kinase (JNK)/c-JUN signalling pathway-related proteins expression were detected by Western blotting. The intracellular calcium content and oxidative stress levels were detected by flow cytometry and reagent kits. Mitochondrial membrane potential was evaluated by tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) staining. The targeting relationship between miR-7a-5p and voltage-dependent anion-selective channel protein 1 (VDAC1) was determined by RNA pull-down assay and dual-luciferase reporter gene assay. The streptozotocin (STZ) rat model was constructed to simulate DPN in vivo. The paw withdrawal mechanical threshold (PTW) was measured by Frey capillary line, and the motor nerve conduction velocity (MNCV) was measured by electromyography. Results: MiR-7a-5p expression was decreased, while VDAC1 expression was increased in HG-induced RSC96 cells and STZ rats. In HG-induced RSC96 cells, miR-7a-5p overexpression promoted cell proliferation, inhibited apoptosis, down-regulated calcium release, improved mitochondrial membrane potential and repressed oxidative stress response. MiR-7a-5p negatively regulated VDAC1 expression. VDAC1 knockdown improved cell proliferation activity, suppressed cell apoptosis and mitochondrial dysfunction by inhibiting JNK/c-JUN pathway activation. MiR-7a-5p overexpression raised PTW, restored MNCV and reduced oxidative stress levels and nerve cell apoptosis in STZ rats. Conclusion: MiR-7a-5p overexpression ameliorated mitochondrial dysfunction and inhibited apoptosis in DPN by regulating VDAC1/JNK/c-JUN pathway.

Expression Profiles of Long Noncoding RNAs and Messenger RNAs in a Rat Model of Spinal Cord Injury

“…In both rat CNS and mouse DRG neurons, JUN-ATF3 dimers promote neurite outgrowth [ 47 ]. A study on diabetes peripheral neuropathy by Jiao et al found that miR-7a-5p regulation ameliorated mitochondrial dysfunction and reduced apoptosis via the VDAC1/JNK/c-JUN pathway [ 48 ]. The SOX10 gene and SOX10 protein are responsible for the gliogenesis of glial cells in neural crest cells [ 49 ].…”

Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway

“…c-Jun plays an important role in the activation of activator protein 1 (AP-1) complex and plays an important role in the transformation process of cell proliferation and differentiation. JNK binds and phosphorylates c-Jun and increases its transcriptional activity, thereby activating an important component of the AP-1 transcription complex, which is an important regulator of gene expression [ 30 – 32 ].…”

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

“…For instance, Feng et al 8 showed that miR-146a levels were markedly blocked in rats with DPN and that miR-146a participates in the pathological process of DPN by regulating inflammatory responses. miR-7a-5p is expressed at low levels in DPN rats and is involved in RSC96 cell proliferation, apoptosis, calcium release, and oxidative stress response, whereas the miR-7a-5p mimic attenuates mitochondrial dysfunction in DPN by modulating VDAC1 expression 9 . The suppression of miRNA-155 can ameliorate sciatic nerve injury in DPN by alleviating inflammation 10 .…”