Abstract：
:Cardiac fibrosis is linked to fibroblast-to-myofibroblast phenoconversion and proliferation but the mechanisms underlying this are poorly understood. Ski is a negative regulator of TGF-β-Smad signaling in myofibroblasts, and might redirect the myofibroblast phenotype back to fibroblasts. Meox2 could alter TGF-β-mediated cellular processes and is repressed by Zeb2. Here, we investigated whether Ski diminishes the myofibroblast phenotype by de-repressing Meox2 expression and function through repression of Zeb2 expression. We show that expression of Meox1 and Meox2 mRNA and Meox2 protein is reduced during phenoconversion of fibroblasts to myofibroblasts. Overexpression of Meox2 shifts the myofibroblasts into fibroblasts, whereas the Meox2 DNA-binding mutant has no effect on myofibroblast phenotype. Overexpression of Ski partially restores Meox2 mRNA expression levels to those in cardiac fibroblasts. Expression of Zeb2 increased during phenoconversion and Ski overexpression reduces Zeb2 expression in first-passage myofibroblasts. Furthermore, expression of Meox2 is decreased in scar following myocardial infarction, whereas Zeb2 protein expression increases in the infarct scar. Thus Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by upregulating the expression of Meox2. This cascade might regulate cardiac myofibroblast phenotype and presents therapeutic options for treatment of cardiac fibrosis.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Cunnington RH,Northcott JM,Ghavami S,Filomeno KL,Jahan F,Kavosh MS,Davies JJ,Wigle JT,Dixon IMdoi
10.1242/jcs.126722subject
Has Abstractpub_date
2014-01-01 00:00:00pages
40-9issue
Pt 1eissn
0021-9533issn
1477-9137pii
jcs.126722journal_volume
127pub_type
杂志文章abstract：:After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and ca...
journal_title：Journal of cell science
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abstract：:SNARE [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor] proteins control the membrane-fusion events of eukaryotic membrane-trafficking pathways. Specific vesicular and target SNAREs operate in specific trafficking routes, but the degree of specificity of SNARE functions is still elus...
journal_title：Journal of cell science
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更新日期：2007-09-15 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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pub_type： 杂志文章,评审
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更新日期：2003-01-01 00:00:00
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更新日期：1992-07-01 00:00:00
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更新日期：2019-07-30 00:00:00
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doi：
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更新日期：2014-08-15 00:00:00
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更新日期：2013-03-01 00:00:00
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更新日期：2013-07-15 00:00:00
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更新日期：2004-11-01 00:00:00
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pub_type： 杂志文章
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更新日期：2013-08-15 00:00:00
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更新日期：2016-11-01 00:00:00
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更新日期：1997-12-01 00:00:00
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更新日期：1998-05-01 00:00:00
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更新日期：1996-02-01 00:00:00
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