PMID- 33333415 OWN - NLM STAT- MEDLINE DCOM- 20210525 LR - 20240226 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 90 DP - 2021 Jan TI - Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1. PG - 107010 LID - S1567-5769(20)30621-4 [pii] LID - 10.1016/j.intimp.2020.107010 [doi] AB - BACKGROUND: Accumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice. METHODS: A mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested. RESULTS: miR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1. CONCLUSION: Functional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Li, Wei AU - Li W AD - Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518000, Guangdong, China. FAU - Jin, Long-Yu AU - Jin LY AD - Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518000, Guangdong, China. FAU - Cui, Yu-Bo AU - Cui YB AD - Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518000, Guangdong, China. FAU - Xie, Ning AU - Xie N AD - Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518000, Guangdong, China. Electronic address: XIEning86u@163.com. LA - eng PT - Journal Article DEP - 20201214 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) RN - 0 (HbA(1c) protein, mouse) RN - 0 (Inflammation Mediators) RN - 0 (MIRN17 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (STAT1 Transcription Factor) SB - IM MH - Animals MH - Apoptosis MH - Blood Glucose/metabolism MH - Cells, Cultured MH - Diabetic Retinopathy/genetics/metabolism/pathology/*therapy MH - Disease Models, Animal MH - Exosomes/genetics/metabolism/*transplantation MH - Glycated Hemoglobin/metabolism MH - Humans MH - Inflammation Mediators/*metabolism MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Mice, Inbred C57BL MH - MicroRNAs/genetics/*metabolism MH - *Oxidative Stress MH - Retina/*metabolism/pathology MH - STAT1 Transcription Factor/genetics/*metabolism MH - Signal Transduction MH - Umbilical Cord/cytology MH - Mice OTO - NOTNLM OT - Diabetic retinopathy OT - Exosomes OT - Signal transducer and activator of transcription 1 OT - microRNA-17-3p EDAT- 2020/12/18 06:00 MHDA- 2021/05/26 06:00 CRDT- 2020/12/17 20:14 PHST- 2020/05/09 00:00 [received] PHST- 2020/09/11 00:00 [revised] PHST- 2020/09/11 00:00 [accepted] PHST- 2020/12/18 06:00 [pubmed] PHST- 2021/05/26 06:00 [medline] PHST- 2020/12/17 20:14 [entrez] AID - S1567-5769(20)30621-4 [pii] AID - 10.1016/j.intimp.2020.107010 [doi] PST - ppublish SO - Int Immunopharmacol. 2021 Jan;90:107010. doi: 10.1016/j.intimp.2020.107010. Epub 2020 Dec 14.