miRNA-1 regulates endothelin-1 in diabetes

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


Aims: 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.

Main methods: 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.

Key findings: 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.

Significance: 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.

Keywords: Endothelial cells; Glucose; MicroRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Diabetes Complications / physiopathology
  • Down-Regulation
  • Endothelial Cells / drug effects
  • Endothelin-1 / genetics*
  • Gene Expression Regulation / drug effects*
  • Glucose / pharmacology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Real-Time Polymerase Chain Reaction
  • Retina / drug effects
  • Umbilical Veins / drug effects


  • Endothelin-1
  • MIRN1 microRNA, human
  • MicroRNAs
  • Mirn1 microRNA, mouse
  • Glucose