Investigation of the role of miR-221 in diabetic peripheral neuropathy and related molecular mechanisms

作者：Xiaole Wu, Xiaoyu Wang, Yiyu Yin, Lei Zhu, Fengchao Zhang, Jianping Yang · 发表于：Advances in Clinical and Experimental Medicine · 年份：2021 · DOI：10.17219/acem/131217 · 被引用次数：23 · 研究领域：Pain Mechanisms and Treatments、Sphingolipid Metabolism and Signaling、Extracellular vesicles in disease

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes, but the molecular mechanisms of DPN are still unclear. OBJECTIVES: To investigate the role of miR-221 in DPN and the related molecular mechanisms. MATERIAL AND METHODS: Streptozotocin (STZ) was used to establish an in vivo DPN model. An in vitro DPN model was established using high glucose-induced SH-SY5Y cells. The pain condition of rats was measured by evaluating the 50% paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Serum exosomes were extracted and identified. Expression of miR-221 in serum exosomes and serum SOCS3 expression were determined using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Western blotting was used to measure the protein levels of SOCS3, bradykinin (BK) and prostaglandin E2 (PEG2). The dual luciferase reporter assay was performed to confirm SOCS3 3'-UTR as a target of miR-221. The serum or cell supernatant levels of PEG2, BK, interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Induction of the lenti-miR-221 inhibitor significantly decreased the expression of miR-221 in DPN rats. Both 50% PWT and PWL values were markedly decreased in DPN rats. When miR-221 was inhibited, the 50% PWT and PWL values were both significantly increased. Knockdown of miR-221 significantly increased the expression of SOCS3 and decreased the express...