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Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization

Alajbegovic, Azra LU ; Turczynska, Karolina LU ; Hien Tran, Thi LU ; Cidad, Pilar; Swärd, Karl LU ; Hellstrand, Per LU ; Corte, Alessandro Della; Forte, Amalia and Albinsson, Sebastian LU (2017) In Biochimica et Biophysica Acta - Molecular Cell Research 1864(6). p.1088-1098
Abstract

The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA.In this study we aimed to determine a profile of miRNAs that were 1) regulated... (More)

The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA.In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells. This analysis was performed using cardiovascular disease-focused miRNA arrays in both mouse and human cells. The potential clinical importance of actin polymerization in aortic aneurysm was evaluated using biopsies from mildly dilated human thoracic aorta in patients with stenotic tricuspid or bicuspid aortic valve.By integrating information from multiple qPCR based miRNA arrays we identified a group of five miRNAs (miR-1, miR-22, miR-143, miR-145 and miR-378a) that were sensitive to actin polymerization and MRTF-A overexpression in both mouse and human vascular smooth muscle. With the exception of miR-22, these miRNAs were also relatively enriched in striated and/or smooth muscle containing tissues. Actin polymerization was found to be dramatically reduced in the aorta from patients with mild aortic dilations. This was associated with a decrease in actin/MRTF-regulated miRNAs.In conclusion, the transcriptional co-activator MRTF-A and actin polymerization regulated a subset of miRNAs in vascular smooth muscle. Identification of novel miRNAs regulated by actin/MRTF-A may provide further insight into the mechanisms underlying vascular disease states, such as aortic aneurysm, as well as novel ideas regarding therapeutic strategies. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Actin polymerization, MicroRNA, MRTF-A, Phenotype, Smooth muscle, Vascular disease
in
Biochimica et Biophysica Acta - Molecular Cell Research
volume
1864
issue
6
pages
1088 - 1098
publisher
Elsevier
external identifiers
  • scopus:85008157645
  • wos:000401682400029
ISSN
0167-4889
DOI
10.1016/j.bbamcr.2016.12.005
language
English
LU publication?
yes
id
7fcc1d58-a26d-4a00-8380-5912d0b28ed9
date added to LUP
2017-01-23 13:29:25
date last changed
2018-10-07 04:51:54
@article{7fcc1d58-a26d-4a00-8380-5912d0b28ed9,
  abstract     = {<p>The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA.In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells. This analysis was performed using cardiovascular disease-focused miRNA arrays in both mouse and human cells. The potential clinical importance of actin polymerization in aortic aneurysm was evaluated using biopsies from mildly dilated human thoracic aorta in patients with stenotic tricuspid or bicuspid aortic valve.By integrating information from multiple qPCR based miRNA arrays we identified a group of five miRNAs (miR-1, miR-22, miR-143, miR-145 and miR-378a) that were sensitive to actin polymerization and MRTF-A overexpression in both mouse and human vascular smooth muscle. With the exception of miR-22, these miRNAs were also relatively enriched in striated and/or smooth muscle containing tissues. Actin polymerization was found to be dramatically reduced in the aorta from patients with mild aortic dilations. This was associated with a decrease in actin/MRTF-regulated miRNAs.In conclusion, the transcriptional co-activator MRTF-A and actin polymerization regulated a subset of miRNAs in vascular smooth muscle. Identification of novel miRNAs regulated by actin/MRTF-A may provide further insight into the mechanisms underlying vascular disease states, such as aortic aneurysm, as well as novel ideas regarding therapeutic strategies. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.</p>},
  author       = {Alajbegovic, Azra and Turczynska, Karolina and Hien Tran, Thi and Cidad, Pilar and Swärd, Karl and Hellstrand, Per and Corte, Alessandro Della and Forte, Amalia and Albinsson, Sebastian},
  issn         = {0167-4889},
  keyword      = {Actin polymerization,MicroRNA,MRTF-A,Phenotype,Smooth muscle,Vascular disease},
  language     = {eng},
  number       = {6},
  pages        = {1088--1098},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Molecular Cell Research},
  title        = {Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization},
  url          = {http://dx.doi.org/10.1016/j.bbamcr.2016.12.005},
  volume       = {1864},
  year         = {2017},
}