MicroRNA-124 inhibits rho associated kinase 1 activity to ameliorate the damages of glomerular endothelial cells caused by high glucose
10.3760/cma.j.issn.1001-7097.2017.01.005
- VernacularTitle: 微小RNA-124通过抑制rho相关蛋白激酶1激活减轻高糖导致的肾小球内皮细胞损伤
- Author:
Mengmeng YIN
1
;
Hui PENG
;
Jielun YANG
;
Qianqian WANG
;
Yuanqing LI
;
Zhijun TAN
;
Dan LUO
;
Tanqi LOU
Author Information
1. Division of Nephrology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathy;
Endothelial cells, glomerular;
MicroRNAs;
rho-associated kinases;
Tight junction proteins
- From:
Chinese Journal of Nephrology
2017;33(1):30-36
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of miR-124-ROCK1 signal pathway in the damages of glomerular endothelial cells (GEnCs) induced by high glucose.
Methods:Rat glomerular endothelial cells were cultured in different glucose concentrations: normal control group (NG: 5.5 mmol/L), high glucose group (HG: 30.0 mmol/L), and cells were treated with ROCK1 inhibitor Y27632, miR-124-3p mimic, miR-124-3p inhibitor. The expressions of ROCK1 activity, cell apotosis and tight junction proteins were detected by Western blot. The cell tight junction protein ZO-1 in those groups were assessed by laser scanning confocal microscope.
Results:High glucose significantly decreased miR-124 expression (P<0.01), ROCK1 activity (P-MYPT1/MYPT1), and cell apoptosis (Cleaved-Caspase3/pro-Caspase3) were found increased while the tight junction proteins ZO-1and Occludin were found decreased in these cells (P<0.05 all P<0.01), However, when pretreated cells with ROCK1 inhibitor Y27632, these injuries were significantly reversed. In cells transfected with miR-124-3p mimic, p-MYPT1/MYPT1 was decreased. p-MYPT1/MYPT1 was however increased in cells transfected with miR-124-3p inhibitor (P<0.05), indicating that miR-124 could directly inhibit ROCK1 activity. The increased ROCK1 activity and apoptosis, as well as the decreased tight junction proteins induced by high glucose were significantly suppressed as miR-124-3p mimic transfected in GEnCs.
Conclusions:According to our experiments, high glucose suppressed miR-124 in glomerular endothelial cells, consequenctly activating ROCK1 activity to damage endothelial cells. MiR-124 overexpression could ameliorate these damages induced by high glucose, suggesting that miR-124 might be a new therapeutic target to prevent glomerular endothelial cells injuries in diabetic nephropathy.
