Distinct effects of voltage-and store-dependent calcium influx on stretch-induced differentiation and growth in vascular smooth muscle.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1665726
- author
- Ren, Jingli LU ; Albinsson, Sebastian LU and Hellstrand, Per LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 285
- issue
- 41
- pages
- 31829 - 31839
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000282764600074
- pmid:20675376
- scopus:77957822445
- pmid:20675376
- 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
- 2016-04-01 10:09:25
- date last changed
- 2022-04-27 19:10:06
@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 = {{American Society for Biochemistry and Molecular Biology}},
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 = {{https://lup.lub.lu.se/search/files/1610234/1710495.pdf}},
doi = {{10.1074/jbc.M109.097576}},
volume = {{285}},
year = {{2010}},
}