Bone marrow mesenchymal stem cells-induced exosomal microRNA-486-3p protects against diabetic retinopathy through TLR4/N
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ORIGINAL ARTICLE
Bone marrow mesenchymal stem cells‑induced exosomal microRNA‑486‑3p protects against diabetic retinopathy through TLR4/ NF‑κB axis repression W. Li1 · L. Jin1 · Y. Cui1 · A. Nie1 · N. Xie1 · G. Liang2 Received: 25 March 2020 / Accepted: 23 August 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract Aim Diabetic retinopathy (DR) is a chronic disease causing health and economic burdens on individuals and society. Thus, this study is conducted to figure out the mechanisms of bone marrow mesenchymal stem cells (BMSCs)-induced exosomal microRNA-486-3p (miR-486-3p) in DR. Methods The putative miR-486-3p binding sites to 3′untranslated region of Toll-like receptor 4 (TLR4) was verified by luciferase reporter assay. High glucose (HG)-treated Muller cells were transfected with miR-486-3p or TLR4-related oligonucleotides and plasmids to explore theirs functions in DR. Additionally, HG-treated Muller cells were co-cultured with BMSC-derived exosomes, exosomes collected from BMSCs that had been transfected with miR-486-3p or TLR4-related oligonucleotides and plasmids to explore their functions in DR. MiR-486-3p, TLR4 and nuclear factor-kappaB (NF-κB) expression, angiogenesis-related factors, oxidative stress factors, viability and apoptosis in HG-treated Muller cells were detected by RT-qPCR, western blot analysis, ELISA, MTT assay and flow cytometry, respectively. Results MiR-486-3p was poorly expressed while TLR4 and NF-κB were highly expressed in HG-treated Muller cells. TLR4 was a target of miR-486-3p. Upregulating miR-486-3p or down-regulating TLR4 inhibited oxidative stress, inflammation and apoptosis, and promoted proliferation of HG-treated Muller cells. Meanwhile, BMSC-derived exosomes inhibited oxidative stress, inflammation and apoptosis, and promoted proliferation of HG-treated Muller cells. Restoring miR-486-3p further enhanced, while up-regulating TLR4 reversed, the improvement of exosomes treatment. Conclusion Our study highlights that up-regulation of miR-486-3p induced by BMSC-derived exosomes played a protective role in DR mice via TLR4/NF-κB axis repression. Keywords Diabetic retinopathy · MicroRNA-486-3p · Bone marrow mesenchymal stem cells · Exosomes · Toll-like receptor 4 · NF-κb signaling pathway
Introduction
* N. Xie [email protected] * G. Liang [email protected] 1
Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, 1017 Dongmen North Road, Luohu District, Shenzhen 518000, Guangdong, China
Department of Ophthalmology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 53300, Guangxi, China
2
Diabetic retinopathy (DR) is conventionally defined as a microvascular disease mainly resulted from the complications of diabetes with profound effects on small blood vessels of the inner retina [1]. The prevalence of DR is specifically estimated to link to diabetes mellitus (DM) [2]. It is listed that DR is attributable to diabetes duration, blood glucose, blood lipids, bod
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