Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-02

AUTHORS

J Mann, F Oakley, F Akiboye, A Elsharkawy, A W Thorne, D A Mann

ABSTRACT

Myofibroblasts are critical cellular elements of wound healing generated at sites of injury by transdifferentiation of resident cells. A paradigm for this process is conversion of hepatic stellate cells (HSC) into hepatic myofibroblasts. Treatment of HSC with DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC) blocked transdifferentiation. 5-azadC also prevented loss of IkappaBalpha and PPARgamma expression that occurs during transdifferentiation to allow acquisition of proinflammatory and profibrogenic characteristics. ChIP analysis revealed IkappaBalpha promoter is associated with transcriptionally repressed chromatin that converts to an active state with 5-azadC treatment. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. siRNA knockdown of MeCP2 elevated IkappaBalpha promoter activity, mRNA and protein expression in myofibroblasts. MeCP2 interacts with IkappaBalpha promoter via a methyl-CpG-dependent mechanism and recruitment into a CBF1 corepression complex. We conclude that MeCP2 and DNA methylation exert epigenetic control over hepatic wound healing and fibrogenesis. More... »

PAGES

4401979

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cdd.4401979

DOI

http://dx.doi.org/10.1038/sj.cdd.4401979

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031115443

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16763620


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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