Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus

Cell Death Dis. 2014 Oct 30;5(10):e1506. doi: 10.1038/cddis.2014.466.


Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Gene Knockdown Techniques
  • Inflammation
  • MAP Kinase Signaling System
  • Mice
  • Neovascularization, Physiologic
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Retinal Vessels / pathology
  • Retinal Vessels / physiopathology
  • Up-Regulation / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • MALAT1 long noncoding RNA, rat
  • Malat1 long non-coding RNA, mouse
  • RNA, Long Noncoding
  • p38 Mitogen-Activated Protein Kinases