Advanced

Stretch-Sensitive Down-Regulation of the miR-144/451 Cluster in Vascular Smooth Muscle and Its Role in AMP-Activated Protein Kinase Signaling.

Turczynska, Karolina LU ; Bhattachariya, Anirban LU ; Säll, Johanna LU ; Göransson, Olga LU ; Swärd, Karl LU ; Hellstrand, Per LU and Albinsson, Sebastian LU (2013) In PLoS ONE 8(5).
Abstract
Vascular smooth muscle cells are constantly exposed to mechanical force by the blood pressure, which is thought to regulate smooth muscle growth, differentiation and contractile function. We have previously shown that the expression of microRNAs (miRNAs), small non-coding RNAs, is essential for regulation of smooth muscle phenotype including stretch-dependent contractile differentiation. In this study, we have investigated the effect of mechanical stretch on miRNA expression and the role of stretch-sensitive miRNAs for intracellular signaling in smooth muscle. MiRNA array analysis, comparing miRNA levels in stretched versus non-stretched portal veins, revealed a dramatic decrease in the miR-144/451 cluster level. Because this miRNA cluster... (More)
Vascular smooth muscle cells are constantly exposed to mechanical force by the blood pressure, which is thought to regulate smooth muscle growth, differentiation and contractile function. We have previously shown that the expression of microRNAs (miRNAs), small non-coding RNAs, is essential for regulation of smooth muscle phenotype including stretch-dependent contractile differentiation. In this study, we have investigated the effect of mechanical stretch on miRNA expression and the role of stretch-sensitive miRNAs for intracellular signaling in smooth muscle. MiRNA array analysis, comparing miRNA levels in stretched versus non-stretched portal veins, revealed a dramatic decrease in the miR-144/451 cluster level. Because this miRNA cluster is predicted to target AMPK pathway components, we next examined activation of this pathway. Diminished miR-144/451 expression was inversely correlated with increased phosphorylation of AMPKα at Thr172 in stretched portal vein. Similar to the effect of stretch, contractile differentiation could be induced in non-stretched portal veins by the AMPK activator, AICAR. Transfection with miR-144/451 mimics reduced the protein expression level of mediators in the AMPK pathway including MO25α, AMPK and ACC. This effect also decreased AICAR-induced activation of the AMPK signaling pathway. In conclusion, our results suggest that stretch-induced activation of AMPK in vascular smooth muscle is in part regulated by reduced levels of miR-144/451 and that this effect may play a role in promoting contractile differentiation of smooth muscle cells. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
5
publisher
Public Library of Science
external identifiers
  • wos:000319330200187
  • pmid:23705032
  • scopus:84877966077
ISSN
1932-6203
DOI
10.1371/journal.pone.0065135
language
English
LU publication?
yes
id
46ad0d8f-b502-4bfb-b213-6cd2e4341ab8 (old id 3804160)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23705032?dopt=Abstract
date added to LUP
2013-06-06 21:36:19
date last changed
2019-04-30 01:59:02
@article{46ad0d8f-b502-4bfb-b213-6cd2e4341ab8,
  abstract     = {Vascular smooth muscle cells are constantly exposed to mechanical force by the blood pressure, which is thought to regulate smooth muscle growth, differentiation and contractile function. We have previously shown that the expression of microRNAs (miRNAs), small non-coding RNAs, is essential for regulation of smooth muscle phenotype including stretch-dependent contractile differentiation. In this study, we have investigated the effect of mechanical stretch on miRNA expression and the role of stretch-sensitive miRNAs for intracellular signaling in smooth muscle. MiRNA array analysis, comparing miRNA levels in stretched versus non-stretched portal veins, revealed a dramatic decrease in the miR-144/451 cluster level. Because this miRNA cluster is predicted to target AMPK pathway components, we next examined activation of this pathway. Diminished miR-144/451 expression was inversely correlated with increased phosphorylation of AMPKα at Thr172 in stretched portal vein. Similar to the effect of stretch, contractile differentiation could be induced in non-stretched portal veins by the AMPK activator, AICAR. Transfection with miR-144/451 mimics reduced the protein expression level of mediators in the AMPK pathway including MO25α, AMPK and ACC. This effect also decreased AICAR-induced activation of the AMPK signaling pathway. In conclusion, our results suggest that stretch-induced activation of AMPK in vascular smooth muscle is in part regulated by reduced levels of miR-144/451 and that this effect may play a role in promoting contractile differentiation of smooth muscle cells.},
  articleno    = {e65135},
  author       = {Turczynska, Karolina and Bhattachariya, Anirban and Säll, Johanna and Göransson, Olga and Swärd, Karl and Hellstrand, Per and Albinsson, Sebastian},
  issn         = {1932-6203},
  language     = {eng},
  number       = {5},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Stretch-Sensitive Down-Regulation of the miR-144/451 Cluster in Vascular Smooth Muscle and Its Role in AMP-Activated Protein Kinase Signaling.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0065135},
  volume       = {8},
  year         = {2013},
}