MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes.
BACKGROUND
In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats.


METHODS
MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenic regulation on MMEVC proliferation and migration was further investigated.


RESULTS
MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration.


CONCLUSIONS
Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats.
Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong, 276003, China.
Zhenjie
Z
Li
Department of General Medicine, Linyi People's Hospital, Linyi, Shandong, 276003, China.
Runxia
R
Jiang
Department of General Medicine, Linyi People's Hospital, Linyi, Shandong, 276003, China.
Qingcai
Q
Yue
Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong, 276003, China. Electronic address: haiying.peng@aol.com.
Haiying
H
Peng
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I
IGF1; MMEVC; Migration; Proliferation; Type 2 diabetes; miR-29