miR-126 promotes angiogenesis and attenuates inflammation after contusion spinal cord injury in rats

Brain Res. 2015 May 22:1608:191-202. doi: 10.1016/j.brainres.2015.02.036. Epub 2015 Feb 24.

Abstract

MicroRNAs are a class of small RNAs that regulate the expression of target mRNAs by inhibiting translation or destabilizing target mRNAs. miR-126 is a microRNA that is highly enriched in endothelial cells. miR-126 has been found to promote angiogenesis and inhibit vascular inflammation in endothelial cells by repressing three target genes Sprouty-related EVH1 domain-containing protein 1 (SPRED1), phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2), and vascular cell adhesion molecule 1 (VCAM1). Our previous study showed that the expression of miR-126 was downregulated after spinal cord injury (SCI). Therefore, we wanted to examine whether upregulation of miR-126 could promote angiogenesis, inhibit inflammation, and exert a positive effect on recovery after contusion SCI. In this study, we found that increased levels of miR-126 promoted angiogenesis, and inhibited leukocyte extravasation into the injured spinal cord, which was concurrent with downregulation of mRNA and protein expression of three validated miR-126 target genes, SPRED1, PIK3R2, and VCAM1. Moreover, a dose-dependent effect of miR-126 was observed in rescuing tissue damage and improving the functional deficit after SCI. Thus, the present study indicated that miR-126 played an important role in angiogenesis and inflammation after SCI.

Keywords: Angiogenesis; Inflammation; Spinal cord injury; miR-126; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cullin Proteins / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Leukocyte Common Antigens / metabolism
  • Leukocytes / drug effects
  • Leukocytes / pathology
  • Locomotion / drug effects
  • Male
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / etiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • RNA, Double-Stranded / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vasopressin / metabolism
  • Repressor Proteins / metabolism
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / pathology
  • Time Factors
  • White Matter / pathology

Substances

  • Cul5 protein, rat
  • Cullin Proteins
  • MIRN126 microRNA, rat
  • MicroRNAs
  • RNA, Double-Stranded
  • Receptors, Vasopressin
  • Repressor Proteins
  • Spred1 protein, rat
  • Phosphatidylinositol 3-Kinases
  • Leukocyte Common Antigens