Vitamin D manipulates miR-181c, miR-20b and miR-15a in human umbilical vein endothelial cells exposed to a diabetic-like environment

Cardiovascular Diabetology

Original Investigation

Metsada Pasmanik-Chor¹  Tali Zitman-Gal²  Janice Green²  Eliezer Golan³  Jacques Bernheim³  Sydney Benchetrit³ 

[1] Bioinformatics Unit, The G. S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel;Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, 44281, Kfar Saba, Israel;Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, 44281, Kfar Saba, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;

关键词: microRNA;    Human umbilical vein endothelial cells;    HUVEC;    Diabetes;    Calcitriol;    Vitamin D;    Endothelial cells;    Diabetic environment;   

DOI  :  10.1186/1475-2840-13-8

 received in 2013-10-11, accepted in 2013-12-11,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundHigh blood and tissue concentrations of glucose and advanced glycation end-products are believed to play an important role in the development of vascular complications in patients with diabetes mellitus (DM) and chronic kidney disease. MicroRNAs (miRNA) are non-coding RNAs that regulate gene expression in a sequence specific manner. MiRNA are involved in various biological processes and become novel biomarkers, modulators and therapeutic targets for diseases such as cancer, atherosclerosis, and DM. Calcitriol (the active form of vitamin D) may inhibit endothelial proliferation, blunt angiogenesis, and be a cardioprotective agent. Calcitriol deficiency is a risk factor for DM and hypertension. The aim of this project was to study the miRNA microarray expression changes in human umbilical vein endothelial cells (HUVEC) treated in a diabetic-like environment with the addition of calcitriol.MethodsHUVEC were treated for 24 h with 200 μg/ml human serum albumin (HSA) and 100 mg/dl glucose (control group) or 200 μg/ml AGE-HSA, and 250 mg/dl glucose (diabetic-like environment), and physiological concentrations (10-10 mol/l) of calcitriol. miRNA microarray analysis and real time PCR to validate the miRNA expression profile and mRNA target gene expression were carried out.ResultsCompared to control, 31 mature human miRNA were differentially expressed in the presence of a diabetic-like environment. Addition of physiological concentrations of calcitriol revealed 39 differentially expressed mature human miRNA. MiR-181c, miR-15a, miR-20b, miR-411, miR-659, miR-126 and miR-510 were selected for further analysis because they are known to be modified in DM and in other biological disorders. The predicted targets of these miRNA (such as KLF6, KLF9, KLF10, TXNIP and IL8) correspond to molecular and biological processes such as immune and defense responses, signal transduction and regulation of RNA.ConclusionThis study identified novel miRNA in the field of diabetic vasculopathy and might provide new information about the effect of vitamin D on gene regulation induced by a diabetic-like environment. New gene targets that are part of the molecular mechanism and the therapeutic treatment in diabetic vasculopathy are highlighted.

【 授权许可】

CC BY   
© Zitman-Gal et al.; licensee BioMed Central Ltd. 2014