Resveratrol Inhibits Diabetic-Induced Müller Cells Apoptosis through MicroRNA-29b/Specificity Protein 1 Pathway.
The aim of this study was to evaluate the anti-apoptosis effects of resveratrol (RSV) on diabetic rats retinal Müller cells in vivo and in vitro and to further investigate the roles of microRNA-29b (miR-29b)/specificity protein 1 (SP1) in the anti-apoptosis mechanism of RSV. Retina was obtained from normal and diabetic rats with or without RSV (5 and 10 mg/kg/day) treatments at 1-7 months. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and Annexin V/PI staining were used to detect apoptosis. Immunofluorescence was used to assess distribution of SP1 in retina. MiR-29b and SP1 messenger RNA (mRNA) expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). SP1, Bax, and bcl-2 protein expression was evaluated by western blotting. Caspase-3 activity was detected by assay kit. Our study showed that the TUNEL-positive cells were mainly localized in the inner nuclear layer (INL) of retina and RSV administration effectively suppressed streptozotocin (STZ)-induced apoptosis of retinal cells in INL in vivo (P < 0.001). Our study also showed that RSV administration effectively suppressed high glucose (HG)-induced retinal Müller cells' apoptosis in vitro (P < 0.001). Furthermore, our study revealed that the diabetes-induced downregulated expression of miR-29b and upregulated expression of SP1 could be rescued by RSV in vivo and in vitro (P < 0.05). The anti-apoptosis effect and downregulated SP1 expression effect of RSV was prevented by miR-29b inhibitor (P < 0.05). MiR-29b mimic increased the above-mentioned effects of RSV (P < 0.001). These findings indicate that RSV is a potential therapeutic option for diabetic retinopathy (DR) and that miR-29b/SP1 pathway play roles in the anti-apoptosis mechanism of RSV.
Department of Clinical Nutrition, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, People's Republic of China. zengkaihong2013@hotmail.com.|School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, People's Republic of China. zengkaihong2013@hotmail.com.
Kaihong
K
Zeng
School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, People's Republic of China.
Yuan
Y
Wang
Institute of Laboratory Animals, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, People's Republic of China.
Na
N
Yang
Department of Neurology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, People's Republic of China.
Duozi
D
Wang
Department of Neurology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, People's Republic of China.
Suping
S
Li
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Jian
J
Ming
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Jing
J
Wang
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Xuemei
X
Yu
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Yi
Y
Song
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Xue
X
Zhou
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Bo
B
Deng
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Xiaona
X
Wu
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Lujiao
L
Huang
School of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
Yongtao
Y
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D063928:Ependymoglial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019270:Fructosamine / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012160:Retina / Q000187:drug effects / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D001786:Blood Glucose; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; D019270:Fructosamine; D053148:Caspase 3; D000077185:Resveratrol
Apoptosis; Diabetic retinopathy; MicroRNA-29b; Müller cells; Resveratrol; Specificity protein 1