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Life Sci. 2014 Mar 7;98(1):18-23. doi: 10.1016/j.lfs.2013.12.199. Epub 2014 Jan 3.

miRNA-1 regulates endothelin-1 in diabetes.

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Department of Pathology, Western University, London, ON, Canada.
Department of Pathology, Western University, London, ON, Canada; Mudanjiang Medical University, China.
Department of Pathology, Western University, London, ON, Canada. Electronic address:



MicroRNAs (miRNAs) play important roles in several biological processes. In this study, we investigated the role of miR-1, an endothelin-1 (ET-1) targeting miRNA, in endothelial cells (ECs) and tissues of diabetic animals. ET-1 is known to be of pathogenetic significance in several chronic diabetic complications.


PCR array was used to identify alterations of miRNA expression in ECs exposed to glucose. miR-1 expression was validated by TaqMan real-time PCR assay. Human retinal ECs (HRECs) and human umbilical vein ECs (HUVECs) exposed to various glucose levels with or without miR-1 mimic transfection, and tissues from streptozotocin-induced diabetic animals after two months of follow-up, were examined for miR-1 expression, as well as ET-1 and fibronectin (FN) mRNA and protein levels.


Array analyses showed glucose-induced alterations of 125 miRNAs (out of 381) in ECs exposed to 25mM glucose compared to 5mM glucose. Fifty-one miRNAs were upregulated and 74 were downregulated. 25mM glucose decreased miR-1 expression and increased ET-1 mRNA and protein levels. miR-1 mimic transfection prevented HG-induced ET-1 upregulation. Furthermore, glucose induced upregulation of FN, which is mediated partly by ET-1, was also prevented by such transfection. Diabetic animals showed decreased miR-1 expression in the retina, heart and kidneys. In parallel, ET-1 mRNA expressions were increased in these tissues of diabetic animals, in association with upregulation of FN.


These results indicate a novel glucose-induced mechanism of tissue damage, in which miR-1 regulates ET-1 expressions in diabetes. Identifying such mechanisms may lead to RNA based treatment for diabetic complications.


Endothelial cells; Glucose; MicroRNA

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