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Similar regulatory mechanisms of caveolins and cavins by myocardin family coactivators in arterial and bladder smooth muscle

Zhu, Baoyi LU ; Rippe, Catarina LU ; Hien Tran, Thi LU ; Zeng, Jianwen LU ; Albinsson, Sebastian LU ; Stenkula, Karin G. LU ; Uvelius, Bengt LU and Swärd, Karl LU (2017) In PLoS ONE 12(5).
Abstract

Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates... (More)

Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates expression of smooth muscle-specific genes, reduced CAV1 and CAV2, whereas the cavins were unaffected or increased. Viral overexpression of MKL1 and myocardin induced caveolin and cavin expression in bladder smooth muscle cells from rats and humans and MYOCD correlated tightly with CAV1 and CAVIN1 in human bladder specimens. A recently described activator of MKL-driven transcription (ISX) failed to induce CAV1/CAVIN1 which may be due to an unusual transactivation mechanism. In all, these findings further support the view that myocardin family coactivators are important transcriptional drivers of caveolins and cavins in smooth muscle.

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publication status
published
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in
PLoS ONE
volume
12
issue
5
publisher
Public Library of Science
external identifiers
  • scopus:85019595096
  • wos:000402062800001
ISSN
1932-6203
DOI
10.1371/journal.pone.0176759
language
English
LU publication?
yes
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fe21adfe-799d-439a-bb68-2468c5518f95
date added to LUP
2017-07-03 17:05:12
date last changed
2017-09-18 11:37:22
@article{fe21adfe-799d-439a-bb68-2468c5518f95,
  abstract     = {<p>Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates expression of smooth muscle-specific genes, reduced CAV1 and CAV2, whereas the cavins were unaffected or increased. Viral overexpression of MKL1 and myocardin induced caveolin and cavin expression in bladder smooth muscle cells from rats and humans and MYOCD correlated tightly with CAV1 and CAVIN1 in human bladder specimens. A recently described activator of MKL-driven transcription (ISX) failed to induce CAV1/CAVIN1 which may be due to an unusual transactivation mechanism. In all, these findings further support the view that myocardin family coactivators are important transcriptional drivers of caveolins and cavins in smooth muscle.</p>},
  articleno    = {e0176759},
  author       = {Zhu, Baoyi and Rippe, Catarina and Hien Tran, Thi and Zeng, Jianwen and Albinsson, Sebastian and Stenkula, Karin G. and Uvelius, Bengt and Swärd, Karl},
  issn         = {1932-6203},
  language     = {eng},
  month        = {05},
  number       = {5},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Similar regulatory mechanisms of caveolins and cavins by myocardin family coactivators in arterial and bladder smooth muscle},
  url          = {http://dx.doi.org/10.1371/journal.pone.0176759},
  volume       = {12},
  year         = {2017},
}