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:
https://lup.lub.lu.se/record/3804160
- author
- Turczynska, Karolina
LU
; Bhattachariya, Anirban
LU
; Säll, Johanna
LU
; Göransson, Olga
LU
; Swärd, Karl
LU
; Hellstrand, Per
LU
and Albinsson, Sebastian
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 8
- issue
- 5
- article number
- e65135
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000319330200187
- pmid:23705032
- scopus:84877966077
- pmid:23705032
- 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
- 2016-04-01 13:12:04
- date last changed
- 2024-03-13 00:27:56
@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.}},
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 (PLoS)}},
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 = {{https://lup.lub.lu.se/search/files/3221181/4219490.pdf}},
doi = {{10.1371/journal.pone.0065135}},
volume = {{8}},
year = {{2013}},
}