MicroRNA-22 regulates inflammation and angiogenesis via targeting VE-cadherin

FEBS Lett. 2017 Feb;591(3):513-526. doi: 10.1002/1873-3468.12565. Epub 2017 Feb 6.

Abstract

The vascular endothelial (VE)-cadherin functions as an endothelial barrier protein controlling endothelial permeability and leukocyte transmigration. Developmental studies indicate that VE-cadherin also plays a vital role in angiogenesis. MicroRNA-22 plays important roles in cardiovascular diseases including cardiac hypertrophy and heart failure. We identified that miR-22 interacts with VE-cadherin mRNA. Overexpression of miR-22 in endothelial cells increases the synthesis of proinflammatory cytokines. Injection of miR-22 results in increased myeloperoxidase activity in the mouse lungs. Moreover, miR-22 injection into the fluorescent-labeled transgenic zebrafish Tg(fli1:EGFP) embryos caused defective vascular development in the dorsal and intersegmental vessels, and vascular markers were significantly suppressed in these embryos. Our studies demonstrate that the conserved targeting of VE-cadherin by miR-22 regulates endothelial inflammation, tissue injury, and angiogenesis.

Keywords: endothelial inflammation; miR-22; vascular development; vascular endothelial-cadherin.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Base Sequence
  • Binding Sites
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Down-Regulation / genetics
  • Embryo, Nonmammalian / metabolism
  • Endothelium / pathology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Inflammation / genetics*
  • Inflammation / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neovascularization, Physiologic / genetics*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Zebrafish / embryology
  • Zebrafish / genetics*

Substances

  • 3' Untranslated Regions
  • Antigens, CD
  • Cadherins
  • MIRN22 microRNA, human
  • MIRN22 microRNA, zebrafish
  • MicroRNAs
  • Mirn22 microRNA, mouse
  • RNA, Messenger
  • cadherin 5