PMID- 35367521 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20220914 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 190 DP - 2022 Aug TI - Extracellular vesicles derived from human umbilical cord mesenchymal stem cells relieves diabetic retinopathy through a microRNA-30c-5p-dependent mechanism. PG - 109861 LID - S0168-8227(22)00673-8 [pii] LID - 10.1016/j.diabres.2022.109861 [doi] AB - AIMS: Extracellular vesicle (EV)-transferred microRNAs (miRNAs) are proved to be potentially therapeutic candidates. Here, we attempted to unveil the role of delivery of miR-30c-5p by human umbilical cord mesenchymal stem cells (hUCMSCs)-derived EVs in diabetic retinopathy (DR). METHODS: miR-30c-5p and PLCG1 expression in streptozotocin-induced diabetes mellitus (DM) rats and high glucose (HG)-treated human retinal endothelial cells (HRECs) was quantified, followed by analysis on their interaction. EVs were isolated from hUCMSCs and co-cultured with HRECs. Through gain- and loss-of-function assays, the role of hUCMSCs-derived EV containing miR-30c-5p in DR involving PLCG1 and NF-kappaB pathway was analyzed in vitro and in vivo. RESULTS: Elevated PLCG1 was found in DM rats and HG-treated HRECs where miR-30c-5p was reduced while increased in hUCMSC-derived EVs. PLCG1 was pinpointed as a target gene of miR-30c-5p, which consequently disrupted the PKC/NF-kappaB pathway. hUCMSC-derived EVs decreased inflammation reaction by transferring miR-30c-5p in DM rats and HG-treated HRECs. Furthermore, similar changing tendency was observed in HG-treated HRECs induced by overexpressed miR-30c-5p through downregulation of PLCG1 in vivo. CONCLUSION: Overall, our findings underlined delivery of miR-30c-5p by hUCMSC-derived EVs as a novel suppressor in the inflammatory response following DR. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - He, Yue AU - He Y AD - Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. Electronic address: hylyfy@163.com. FAU - Zhang, Zhiru AU - Zhang Z AD - Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. FAU - Yao, Tianyu AU - Yao T AD - Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. FAU - Huang, Li AU - Huang L AD - Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. FAU - Gan, Jinhua AU - Gan J AD - Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. FAU - Lv, Hongbin AU - Lv H AD - Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. FAU - Chen, Jie AU - Chen J AD - Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, PR China. Electronic address: cjlion@qq.com. LA - eng PT - Journal Article DEP - 20220401 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (MicroRNAs) RN - 0 (NF-kappa B) SB - IM MH - Animals MH - *Diabetes Mellitus/metabolism MH - *Diabetic Retinopathy/genetics/metabolism/therapy MH - Endothelial Cells/metabolism MH - *Extracellular Vesicles/metabolism MH - Humans MH - *Mesenchymal Stem Cells/metabolism MH - *MicroRNAs/genetics/metabolism MH - NF-kappa B/metabolism MH - Rats MH - Umbilical Cord/metabolism OTO - NOTNLM OT - Diabetic retinopathy OT - Extracellular vesicles OT - Human umbilical cord mesenchymal stem cells OT - PKC/NF-kappaB pathway OT - PLCG1 OT - microRNA-30c-5p COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/04/04 06:00 MHDA- 2022/09/09 06:00 CRDT- 2022/04/03 20:25 PHST- 2021/11/18 00:00 [received] PHST- 2022/03/25 00:00 [revised] PHST- 2022/03/29 00:00 [accepted] PHST- 2022/04/04 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/04/03 20:25 [entrez] AID - S0168-8227(22)00673-8 [pii] AID - 10.1016/j.diabres.2022.109861 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2022 Aug;190:109861. doi: 10.1016/j.diabres.2022.109861. Epub 2022 Apr 1.