PMID- 33958320 OWN - NLM STAT- Publisher LR - 20240222 IS - 2530-0180 (Electronic) IS - 2530-0180 (Linking) DP - 2021 May 3 TI - miR-125a-5p in astrocytes attenuates peripheral neuropathy in type 2 diabetic mice through targeting TRAF6. LID - S2530-0164(21)00104-X [pii] LID - 10.1016/j.endinu.2021.01.007 [doi] AB - INTRODUCTION: Elimination or blocking of astrocytes could ameliorate neuropathic pain in animal models. MiR-125a-5p, expressed in astrocyte derived extracellular vesicles, could mediate astrocyte function to regulate neuron communication. However, the role of miR-125a-5p in DPN (diabetic peripheral neuropathy) remains elusive. MATERIALS AND METHODS: Type 2 diabetic mouse (db/db) was used as DPN model, which was confirmed by detection of body weight, blood glucose, mechanical allodynia, thermal hyperalgesia, glial fibrillary acidic protein (GFAP) and monocyte chemoattractant protein-1 (MCP-1). Astrocyte was isolated from db/db mouse and then subjected to high glucose treatment. The expression of miR-125a-5p in db/db mice and high glucose-induced astrocytes was examined by qRT-PCR analysis. Downstream target of miR-125a-5p was clarified by luciferase reporter assay. Tail vein injection of miR-125a-5p mimic into db/db mice was then performed to investigate role of miR-125a-5p on DPN. RESULTS: Type 2 diabetic mice showed higher body weight and blood glucose than normal db/m mice. Thermal hyperalgesia and mechanical allodynia were decreased in db/db mouse compared with db/m mouse, while GFAP and MCP-1 were increased in db/db mouse. High glucose treatment enhanced the protein expression of GFAP and MCP-1 in astrocytes. Sciatic nerve tissues in db/db mice and high glucose-induced astrocytes exhibited a decrease in miR-125a-5p. Systemic administration of miR-125a-5p mimic increased mechanical allodynia and thermal hyperalgesia, whereas it decreased GFAP and MCP-1. TRAF6 (tumor necrosis factor receptor associated factor 6) was validated as target of miR-125a-5p. CONCLUSION: MiR-125a-5p in astrocytes attenuated DPN in db/db mice by up-regulation of TRAF6, which indicated the potential therapeutic effect. CI - Copyright (c) 2021 SEEN y SED. Publicado por Elsevier Espana, S.L.U. All rights reserved. FAU - Kasimu, Aziguli AU - Kasimu A AD - Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi City, Xinjiang Uygur Autonomous Region 830001, China. FAU - Apizi, Xierenguli AU - Apizi X AD - Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi City, Xinjiang Uygur Autonomous Region 830001, China. FAU - Talifujiang, Dilibaier AU - Talifujiang D AD - Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi City, Xinjiang Uygur Autonomous Region 830001, China. FAU - Ma, Xin AU - Ma X AD - Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi City, Xinjiang Uygur Autonomous Region 830001, China. FAU - Fang, Liping AU - Fang L AD - Department of Endocrinology, Honghu People's Hospital, Jingzhou City, Hubei Province 433200, China. FAU - Zhou, Xiangling AU - Zhou X AD - Department of Neurology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province 430081, China. Electronic address: zhouxiangling1123@163.com. LA - eng LA - spa PT - Journal Article DEP - 20210503 PL - Spain TA - Endocrinol Diabetes Nutr (Engl Ed) JT - Endocrinologia, diabetes y nutricion JID - 101717565 SB - IM OTO - NOTNLM OT - Astrocitos OT - Astrocytes OT - Diabetic mice OT - Diabetic peripheral neuropathy OT - Neuropatia periferica diabetica OT - Ratones diabeticos OT - TRAF6 OT - miR-125a-5p EDAT- 2021/05/08 06:00 MHDA- 2021/05/08 06:00 CRDT- 2021/05/07 06:31 PHST- 2020/11/23 00:00 [received] PHST- 2021/01/10 00:00 [revised] PHST- 2021/01/14 00:00 [accepted] PHST- 2021/05/07 06:31 [entrez] PHST- 2021/05/08 06:00 [pubmed] PHST- 2021/05/08 06:00 [medline] AID - S2530-0164(21)00104-X [pii] AID - 10.1016/j.endinu.2021.01.007 [doi] PST - aheadofprint SO - Endocrinol Diabetes Nutr (Engl Ed). 2021 May 3:S2530-0164(21)00104-X. doi: 10.1016/j.endinu.2021.01.007.