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MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle

Hien, Tran T. LU ; Garcia-Vaz, Eliana LU ; Stenkula, Karin G. LU ; Sjögren, Johan LU ; Nilsson, Johan LU ; Gomez, Maria F. LU and Albinsson, Sebastian LU (2018) In Journal of Cellular Physiology
Abstract

Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were... (More)

Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were found in arteries of diabetic mice and patients. This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation of KLF4, the induction of smooth muscle contractile protein markers by glucose was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic conditions contributes to increased expression of contractile markers in vascular smooth muscle cells. Further studies are warranted to determine the therapeutic implications of miR-29 inhibition in diabetic vascular disease.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Contractile differentiation, Glucose, MicroRNA, Vascular smooth muscle
in
Journal of Cellular Physiology
publisher
John Wiley & Sons
external identifiers
  • scopus:85044389057
ISSN
0021-9541
DOI
10.1002/jcp.26549
language
English
LU publication?
yes
id
af4bf656-a603-4346-a8d4-347f2146a701
date added to LUP
2018-04-09 13:53:46
date last changed
2018-07-10 03:00:35
@article{af4bf656-a603-4346-a8d4-347f2146a701,
  abstract     = {<p>Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were found in arteries of diabetic mice and patients. This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation of KLF4, the induction of smooth muscle contractile protein markers by glucose was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic conditions contributes to increased expression of contractile markers in vascular smooth muscle cells. Further studies are warranted to determine the therapeutic implications of miR-29 inhibition in diabetic vascular disease.</p>},
  author       = {Hien, Tran T. and Garcia-Vaz, Eliana and Stenkula, Karin G. and Sjögren, Johan and Nilsson, Johan and Gomez, Maria F. and Albinsson, Sebastian},
  issn         = {0021-9541},
  keyword      = {Contractile differentiation,Glucose,MicroRNA,Vascular smooth muscle},
  language     = {eng},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Cellular Physiology},
  title        = {MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle},
  url          = {http://dx.doi.org/10.1002/jcp.26549},
  year         = {2018},
}