Dataset Information

A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats.

ABSTRACT:

Background

Myofibroblast differentiation is a key event during wound healing and is triggered primarily by transforming growth factor beta (TGFbeta). Serum response factor (SRF) is a TGFbeta-inducible transcription factor that is important for wound healing. Injection of SRF expression plasmid into rat gastric ulcers significantly accelerated restoration of epithelium and smooth muscle structures.

Aim

To determine the role of SRF in oesophageal ulcer healing, especially in myofibroblast differentiation.

Subjects

Rats (in vivo), oesophageal epithelial cells (Het1A) and fibroblasts (Rat1-R12) (in vitro) were used.

Methods

Oesophageal ulcers were induced in rats with acetic acid and subsequently treated by local injection of plasmids expressing either SRF or SRF antisense sequence. Rats were killed at 1, 3, 6, 9 and 14 days after treatment and tissues collected. For in vitro studies, both Het1A and Rat1-R12 cells were transfected with the plasmids used in ulcer treatment.

Results

Upregulation of SRF increased the myofibroblast population in ulcer granulation tissue; knockdown of SRF suppressed this event. In addition, ulceration induced SRF and TGFbeta expression coordinately. In vitro studies showed that overexpression of SRF in either oesophageal epithelial cells or fibroblasts was sufficient to induce myofibroblast phenotype. Furthermore, the TGFbeta-induced myofibroblast phenotype required integrin-linked kinase (ILK)-mediated SRF activation, as either knockdown of SRF or inactivation of ILK prevented this action.

Conclusions

SRF is indispensable for myofibroblast differentiation during oesophageal ulcer healing and is required for TGFbeta-induced myofibroblast transition from either epithelial cells or fibroblasts. ILK is a mediator in TGFbeta-induced SRF activation and subsequent myofibroblast differentiation. ILK is associated with SRF, and TGFbeta enhances this association.

SUBMITTER: Chai J

PROVIDER: S-EPMC1942159 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Publications

A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats.

Chai Jianyuan J Norng Manith M Tarnawski Andrzej S AS Chow Justine J

Gut 20061026 5

<h4>Background</h4>Myofibroblast differentiation is a key event during wound healing and is triggered primarily by transforming growth factor beta (TGFbeta). Serum response factor (SRF) is a TGFbeta-inducible transcription factor that is important for wound healing. Injection of SRF expression plasmid into rat gastric ulcers significantly accelerated restoration of epithelium and smooth muscle structures.<h4>Aim</h4>To determine the role of SRF in oesophageal ulcer healing, especially in myofibr ...[more]

PMID: 17068115

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Dataset Information

A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats.

Background

Aim

Subjects

Methods

Results

Conclusions

Publications

A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats.

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