Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.727
Index Copernicus  – 152.95 pts
MNiSW – 40 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

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doi: 10.17219/acem/131217

Publication type: original article

Language: English

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

Xiaole Wu1,2,A,B,C,D,E,F, Xiaoyu Wang3,B,C,E,F, Yiyu Yin4,B,C,E,F, Lei Zhu5,B,C,E,F, Fengchao Zhang2,B,C,E,F, Jianping Yang1,C,E,F

1 Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, China

2 Department of Anesthesiology, Xuzhou Children’s Hospital, Xuzhou Medical University, China

3 Department of Thoracic Surgery, Xuzhou Children’s Hospital, Xuzhou Medical University, China

4 Department of General Surgery, Xuzhou Children’s Hospital, Xuzhou Medical University, China

5 Intensive Care Unit, Xuzhou Children’s Hospital, Xuzhou Medical University, China

Abstract

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 expression of NF-κB. Furthermore, knockdown of miR-221 remarkably decreased the expression of PEG2, BK, IL-6, IL-1β, and TNF-α in both STZ-treated DPN rats and high glucose-induced SH-SY5Y cells, which was reversed by inhibition of SOCS3. The dual luciferase reporter assay showed that miR-221 directly targeted and negatively regulated SOCS3.
Conclusion. Inhibition of miR-221 can reduce pain and decrease expression of inflammatory factors through targeting SOCS3 in DPN.

Key words

exosomes, miR-221, SOCS3, diabetic peripheral neuralgia

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