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Distinct effects of voltage-and store-dependent calcium influx on stretch-induced differentiation and growth in vascular smooth muscle.

Ren, Jingli LU ; Albinsson, Sebastian LU and Hellstrand, Per LU (2010) In Journal of Biological Chemistry 285(41). p.31829-31839
Abstract
Stretch of the vascular wall stimulates smooth muscle hypertrophy by activating the MAPK and Rho/Rho kinase (ROK) pathways. We investigated the role of calcium in this response. Stretch-stimulated expression of contractile and cytoskeletal proteins in mouse portal vein was inhibited at mRNA and protein levels by blockade of voltage-dependent Ca(2+) entry (VDCE). In contrast, blockade of store-operated Ca(2+) entry (SOCE) did not affect smooth muscle marker expression but decreased global protein synthesis. Activation of VDCE caused membrane translocation of RhoA followed by phosphorylation of its downstream effectors LIMK-2 and cofilin-2. Stretch-activated cofilin-2 phosphorylation depended on VDCE but not on SOCE. VDCE was associated with... (More)
Stretch of the vascular wall stimulates smooth muscle hypertrophy by activating the MAPK and Rho/Rho kinase (ROK) pathways. We investigated the role of calcium in this response. Stretch-stimulated expression of contractile and cytoskeletal proteins in mouse portal vein was inhibited at mRNA and protein levels by blockade of voltage-dependent Ca(2+) entry (VDCE). In contrast, blockade of store-operated Ca(2+) entry (SOCE) did not affect smooth muscle marker expression but decreased global protein synthesis. Activation of VDCE caused membrane translocation of RhoA followed by phosphorylation of its downstream effectors LIMK-2 and cofilin-2. Stretch-activated cofilin-2 phosphorylation depended on VDCE but not on SOCE. VDCE was associated with increased mRNA expression of myocardin, myocyte enhancer factor (MEF) -2A and -2D and smooth muscle marker genes, all of which depended on ROK activity. SOCE increased ERK1/2 phosphorylation and c-fos expression but had no effect on phosphorylation of LIMK-2 and cofilin-2 or on myocardin and MEF2 expression. Knock-down of MEF2A or -2D eliminated the VDCE-induced activation of myocardin expression and increased basal c-jun and c-fos mRNA levels. These results indicate that MEF2 mediates VDCE-dependent stimulation of myocardin expression via the Rho/ROK pathway. In addition, SOCE activates the expression of immediate-early genes, known to be regulated by MEF2 via Ca(2+)-dependent phosphorylation of histone deacetylases, but this mode of Ca(2+) entry does not affect the Rho/ROK pathway. Compartmentation of Ca(2+) entry pathways appears as one mechanism whereby extracellular and membrane signals influence smooth muscle phenotype regulation, with MEF2 as a focal point. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
285
issue
41
pages
31829 - 31839
publisher
ASBMB
external identifiers
  • wos:000282764600074
  • pmid:20675376
  • scopus:77957822445
ISSN
1083-351X
DOI
10.1074/jbc.M109.097576
language
English
LU publication?
yes
id
bca0b5d7-b00f-4828-8fb2-ed3d87fe7990 (old id 1665726)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20675376?dopt=Abstract
date added to LUP
2010-09-02 09:23:57
date last changed
2018-06-24 03:10:09
@article{bca0b5d7-b00f-4828-8fb2-ed3d87fe7990,
  abstract     = {Stretch of the vascular wall stimulates smooth muscle hypertrophy by activating the MAPK and Rho/Rho kinase (ROK) pathways. We investigated the role of calcium in this response. Stretch-stimulated expression of contractile and cytoskeletal proteins in mouse portal vein was inhibited at mRNA and protein levels by blockade of voltage-dependent Ca(2+) entry (VDCE). In contrast, blockade of store-operated Ca(2+) entry (SOCE) did not affect smooth muscle marker expression but decreased global protein synthesis. Activation of VDCE caused membrane translocation of RhoA followed by phosphorylation of its downstream effectors LIMK-2 and cofilin-2. Stretch-activated cofilin-2 phosphorylation depended on VDCE but not on SOCE. VDCE was associated with increased mRNA expression of myocardin, myocyte enhancer factor (MEF) -2A and -2D and smooth muscle marker genes, all of which depended on ROK activity. SOCE increased ERK1/2 phosphorylation and c-fos expression but had no effect on phosphorylation of LIMK-2 and cofilin-2 or on myocardin and MEF2 expression. Knock-down of MEF2A or -2D eliminated the VDCE-induced activation of myocardin expression and increased basal c-jun and c-fos mRNA levels. These results indicate that MEF2 mediates VDCE-dependent stimulation of myocardin expression via the Rho/ROK pathway. In addition, SOCE activates the expression of immediate-early genes, known to be regulated by MEF2 via Ca(2+)-dependent phosphorylation of histone deacetylases, but this mode of Ca(2+) entry does not affect the Rho/ROK pathway. Compartmentation of Ca(2+) entry pathways appears as one mechanism whereby extracellular and membrane signals influence smooth muscle phenotype regulation, with MEF2 as a focal point.},
  author       = {Ren, Jingli and Albinsson, Sebastian and Hellstrand, Per},
  issn         = {1083-351X},
  language     = {eng},
  number       = {41},
  pages        = {31829--31839},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Distinct effects of voltage-and store-dependent calcium influx on stretch-induced differentiation and growth in vascular smooth muscle.},
  url          = {http://dx.doi.org/10.1074/jbc.M109.097576},
  volume       = {285},
  year         = {2010},
}