Back to Search
Start Over
MiR-18a-5p inhibits endothelial-mesenchymal transition and cardiac fibrosis through the Notch2 pathway.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Sep 16; Vol. 491 (2), pp. 329-336. Date of Electronic Publication: 2017 Jul 19. - Publication Year :
- 2017
-
Abstract
- Hyperglycemia plays a crucial role in the pathogenesis of diabetic complications; however, the mechanisms underlying diabetic cardiac fibrosis remain unclear. Endothelial cells are known to contribute to cardiac fibrosis through endothelial-mesenchymal transition (EndMT) under high glucose stimulation. Here we investigated the expression of miR-18a-5p and examined its functional role in human aortic valvular endothelial cells (HAVECs). Using HAVECs, we revealed that miR-18a-5p regulated high glucose-induced EndMT. Moreover, high glucose levels induced Notch2 expression, which promoted EndMT, resulting in the downregulation of vascular endothelial cadherin and CD31 and upregulation of fibroblast-specific protein-1, α-smooth muscle actin, fibronectin, and vimentin. Furthermore, Notch2 was identified as a target of miR-18a-5p. Our data showed that the overexpression of miR-18a-5p could downregulate Notch2 expression and subsequently suppress EndMT. In conclusion, our findings demonstrated that miR-18a-5p/Notch2 signaling pathway participates in the regulation of high glucose-induced EndMT, and may act as a novel promising target for myocardial fibrosis in diabetic cardiomyopathy.<br /> (Copyright © 2017. Published by Elsevier Inc.)
- Subjects :
- Actins genetics
Actins metabolism
Animals
Aortic Valve cytology
Aortic Valve drug effects
Aortic Valve metabolism
Cadherins genetics
Cadherins metabolism
Calcium-Binding Proteins genetics
Calcium-Binding Proteins metabolism
Cell Line
Dependovirus metabolism
Diabetes Mellitus, Experimental chemically induced
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental pathology
Diabetic Cardiomyopathies chemically induced
Diabetic Cardiomyopathies pathology
Diabetic Cardiomyopathies prevention & control
Endomyocardial Fibrosis chemically induced
Endomyocardial Fibrosis pathology
Endomyocardial Fibrosis prevention & control
Endothelial Cells cytology
Endothelial Cells drug effects
Endothelial Cells metabolism
Fibronectins genetics
Fibronectins metabolism
Gene Expression Regulation
Genetic Vectors administration & dosage
Genetic Vectors chemistry
Genetic Vectors metabolism
Glucose pharmacology
Heart Ventricles metabolism
Heart Ventricles pathology
Humans
Male
Mice, Inbred C57BL
MicroRNAs metabolism
Platelet Endothelial Cell Adhesion Molecule-1 genetics
Platelet Endothelial Cell Adhesion Molecule-1 metabolism
Receptor, Notch2 metabolism
S100 Calcium-Binding Protein A4
Signal Transduction
Streptozocin
Vimentin genetics
Vimentin metabolism
Dependovirus genetics
Diabetic Cardiomyopathies genetics
Endomyocardial Fibrosis genetics
Epithelial-Mesenchymal Transition
MicroRNAs genetics
Receptor, Notch2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 491
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 28733035
- Full Text :
- https://doi.org/10.1016/j.bbrc.2017.07.101