MicroRNA-148a-3p alleviates high glucose-induced diabetic retinopathy by targeting TGFB2 and FGF2
- PDF / 4,334,897 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 85 Downloads / 171 Views
ORIGINAL ARTICLE
MicroRNA‑148a‑3p alleviates high glucose‑induced diabetic retinopathy by targeting TGFB2 and FGF2 Jihong Wang1 · Yong Yao2 · Kelei Wang3 · Jia Li1 · Ting Chu1 · Haicui Shen1 Received: 25 May 2020 / Accepted: 30 June 2020 © Springer-Verlag Italia S.r.l., part of Springer Nature 2020
Abstract Aims Diabetic retinopathy (DR), a common complication of type 1 or type 2 diabetes mellitus, has become the leading cause of blindness among adults in working age. The dysregulation of microRNA has been reported to be strongly related to the initiation or progression of DR. However, neither the biological role nor the molecular mechanism of miR-148a-3p has been researched in DR. This study is designed to investigate the function and mechanism of miR-148a-3p in DR. Methods The bioinformatics analysis (Targetscan: https://www.targetscan.org/vert_72/) and numerous experiments including real-time quantitative polymerase chain reaction, terminal deoxynucleotidyltransferase dUTP nick end labeling, CCK-8, western blot, vasculogenesis and luciferase reporter assays were used to research the function and mechanism of miR-148a-3p in DR. Results We constructed DR cell model by treating human retinal microvascular endothelial cells (HRECs) with different concentration gradients of high glucose (HG). Additionally, HG treatment reduced miR-148a-3p level in HRECs. In function, overexpression of miR-148a-3p caused an increase in cell viability and a decrease in cell apoptosis. Besides, miR-148a-3p overexpression led to a damage on blood–retinal barrier (BRB) and suppressed angiogenesis. In mechanism, miR-148a-3p specifically bound to 3′ untranslated region of TGFB2 and FGF2. At least, rescue assays demonstrated that the inhibitive influence of miR-148a-3p mimics on BRB injury was offset by overexpression of TGFB2 and the attenuation of angiogenesis resulting from miR-148a-3p mimics was abrogated by overexpression of FGF2 Conclusions In a word, we discovered that miR-148a-3p alleviated HG-induced DR by targeting TGFB2 and FGF2. This novel discovery indicated miR-148a-3p as a potential target for DR diagnosis or treatment. Keywords MiR-148a-3p · Diabetic retinopathy · TGFB2 · FGF2
Introduction
This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques. * Jihong Wang [email protected] 1
Department of Ophthalmology, Affiliated Hospital of Jiangnan University, No. 200 Huihe Road, Wuxi 214000, Jiangsu, China
2
Department of Ophthalmology, Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi 214000, Jiangsu, China
3
Department of Ophthalmology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi 214000, Jiangsu, China
Diabetes mellitus, a prevalent chronic disease, is characterized by hyperglycemia and neurovascular damage because of the lack of insulin [1]. Diabetic retinopathy (DR), a common complication of type 1 or type 2 diabetes mellitus, has become the leading cause of blindness among adults in working age [2, 3]. The blood–retinal ba
Data Loading...
