PMID- 34655847 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20220321 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 101 IP - Pt B DP - 2021 Dec TI - Extracellular vesicles secreted from mesenchymal stem cells exert anti-apoptotic and anti-inflammatory effects via transmitting microRNA-18b in rats with diabetic retinopathy. PG - 108234 LID - S1567-5769(21)00870-5 [pii] LID - 10.1016/j.intimp.2021.108234 [doi] AB - Diabetic retinopathy (DR) is a major cause of visual deficits and blindness in the working-age population and inflammatory response is a key event during DR. In this study, we investigated the anti-inflammatory properties of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in a diabetic rat model and human retinal microvascular endothelial cells. After development of DR in rats subjected to diabetes induction with streptozotocin (STZ), the DR rats were treated with different concentrations of hUCMSC-sEVs. Our results showed that the treatment of the retinas of DR rats with hUCMSC-sEVs not only reduced the level of vascular leakage in the retinas of rats but also decreased the retinal thickness as well as the associated inflammation. Further, our in vitro evidences suggest that hUCMSC-sEVs repress high glucose (HG)-induced cell inflammation and apoptosis. Subsequently, we analyzed the differentially expressed microRNAs (miRNAs) in the hUCMSC-sEVs by microarray and performed in silico studies to predict the target mRNA of miR-18b. Our findings also revealed that the expression of miR-18b was significantly elevated in the retina of diabetic rats after sEV treatment. In addition, miR-18b was found to target mitogen-activated protein kinase kinase kinase 1 (MAP3K1), thereby inhibiting NF-kappaB p65 phosphorylation to alleviate DR. Overall, this study highlights the potential of hUCMSCs-sEVs as biomaterials for anti-inflammatory and anti-apoptotic effects in DR by transferring miR-18b. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Xu, Zepeng AU - Xu Z AD - Department of Ophthalmology, Jiangmen Wuyi Hospital of TCM, Jiangmen 529000, Guangdong, China; The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China. FAU - Tian, Ni AU - Tian N AD - Department of Ophthalmology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China. Electronic address: tianni5191@126.com. FAU - Li, Songtao AU - Li S AD - The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China. FAU - Li, Kunmeng AU - Li K AD - The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China. FAU - Guo, Haike AU - Guo H AD - Department of Ophthalmology, Shanghai Heping Eye Hospital, Shanghai 200437, China. FAU - Zhang, Hongyang AU - Zhang H AD - Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangzhou 510120, Guangdong, China. FAU - Jin, Haiying AU - Jin H AD - Department of Ophthalmology, Shanghai No. 10 People's Hospital, Shanghai 200040, China. FAU - An, Meixia AU - An M AD - Department of Ophthalmology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, China. FAU - Yu, Xiaoyi AU - Yu X AD - Department of Ophthalmology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China. LA - eng PT - Journal Article DEP - 20211013 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Blood Glucose) RN - 0 (MIRN18 microRNA, rat) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - *Apoptosis MH - Aqueous Humor MH - Blood Glucose MH - Diabetes Mellitus, Experimental/complications MH - Diabetic Retinopathy/*therapy MH - *Extracellular Vesicles MH - Inflammation/*therapy MH - Male MH - Mesenchymal Stem Cells/*physiology MH - MicroRNAs/genetics/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Retina/pathology OTO - NOTNLM OT - Diabetic retinopathy OT - Human umbilical cord mesenchymal stem cells OT - MAP3K1 OT - NF-kappaB p65 OT - Small extracellular vesicles OT - microRNA-18b EDAT- 2021/10/17 06:00 MHDA- 2022/03/22 06:00 CRDT- 2021/10/16 20:15 PHST- 2021/06/15 00:00 [received] PHST- 2021/09/14 00:00 [revised] PHST- 2021/10/04 00:00 [accepted] PHST- 2021/10/17 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2021/10/16 20:15 [entrez] AID - S1567-5769(21)00870-5 [pii] AID - 10.1016/j.intimp.2021.108234 [doi] PST - ppublish SO - Int Immunopharmacol. 2021 Dec;101(Pt B):108234. doi: 10.1016/j.intimp.2021.108234. Epub 2021 Oct 13.