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

Jianyuan Chai; Norng, Manith; Tarnawski, Andrzej S.; Chow, Justine
May 2007
Gut;May2007, Vol. 56 Issue 5, p621
Academic Journal
Background: Myofibroblast differentiation is a key event during wound healing and is triggered primarily by transforming growth factor β (TGFβ). Serum response factor (SRF) is a TGFβ-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 TGFβ 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 TGFI3-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 TGFβ-induced myofibroblast transition from either epithelial cells or fibroblasts. ILK is a mediator in TGFβ-induced SRF activation and subsequent myofibroblast differentiation. ILK is associated with SRF, and TGFβ enhances this association.


Related Articles

  • Rat as an animal model for Peyronie's disease research: a review of current methods and the peer-reviewed literature. Chung, E; De Young, L; Brock, G B // International Journal of Impotence Research;Nov/Dec2011, Vol. 23 Issue 6, p235 

    While the exact mechanism of Peyronie's disease (PD) remains an enigma, the pathophysiology of PD is considered to be multifactorial, with interactions of genetic predisposition, trauma, tissue inflammation and aberrant wound healing. A non-systematic review of the existing English language...

  • Inducible Lineage-Specific Deletion of TβRII in Fibroblasts Defines a Pivotal Regulatory Role during Adult Skin Wound Healing. Denton, Christopher P.; Khan, Korsa; Hoyles, Rachel K.; Shiwen, Xu; Leoni, Patricia; Chen, Yunliang; Eastwood, Mark; Abraham, David J. // Journal of Investigative Dermatology;Jan2009, Vol. 129 Issue 1, p194 

    Previous attempts to delete type II TGFβ receptor (TβRII) in fibroblasts have precluded examination of adult mice due to early mortality. We have selectively deleted TβRII postnatally in differentiated connective tissue fibroblasts using an inducible Cre-Lox strategy....

  • Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Mann, J.; Oakley, F.; Akiboye, F.; Elsharkawy, A.; Thorne, A. W.; Mann, D. A. // Cell Death & Differentiation;Feb2007, Vol. 14 Issue 2, p275 

    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...

  • Cyclosporin A-induced gingival overgrowth is not associated with myofibroblast transdifferentiation. Sobral, Lays Martin; Kellermann, Michele Gassen; Graner, Edgard; Martelli-Junior, Hercilio; Coletta, Ricardo Della // Brazilian Oral Research;Apr-Jun2010, Vol. 24 Issue 2, p182 

    Cyclosporin A (CyA) induces gingival overgrowth via its stimulatory effects on expression of transforming growth factor-beta1 (TGF-β1) and collagen. It is not known whether CyA has a direct effect on gingival fibroblasts or induces its effect indirectly via stimulation of myofibroblast...

  • Extracorporeal Shock Wave Treatment Improves Incisional Wound Healing in Diabetic Rats. Guang Yang; Congfeng Luo; Xiaoyu Yan; Liang Cheng; Yimin Chai // Tohoku Journal of Experimental Medicine;Dec2011, Vol. 225 Issue 4, p285 

    Impaired wound healing in surgical patients with diabetes increases the incidence of infection, prolongs hospitalization, and even increases the rate of mortality. Low-energy extracorporeal shock wave treatment (ESWT) was reported to accelerate chronic wound healing by promoting...

  • Evidence for Apoptosis Induction in Myofibroblasts during Palatal Mucoperiosteal Repair. Funato, N.; Moriyama, K.; Baba, Y.; Kuroda, T. // Journal of Dental Research;Sep1999, Vol. 78 Issue 9, p1511 

    Apoptosis is thought to be a requisite event for maintaining kinetic homeostasis within continually renewing tissues such as the oral mucosa and skin. However, no systematic study of the apoptotic process in fibroblasts in the oral mucosa following injury has been performed. In this study, we...

  • Cell Adhesion and Shape Regulate TGF-Beta1-Induced Epithelial-Myofibroblast Transition via MRTF-A Signaling. O’Connor, Joseph W.; Gomez, Esther W. // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Myofibroblasts, specialized cells that play important roles in wound healing and fibrosis, can develop from epithelial cells through an epithelial-mesenchymal transition (EMT). During EMT, epithelial cells detach from neighboring cells and acquire an elongated, mesenchymal-like morphology. These...

  • Acceleration of Palatal Wound Healing in Smad3-deficient Mice. Jinno, K.; Takahashi, T.; Tsuchida, K.; Tanaka, E.; Moriyama, K. // Journal of Dental Research;Aug2009, Vol. 88 Issue 8, p757 

    Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that transforming growth factor (TGF)-β/Smad3 signaling is involved in wound healing. The purpose of this study was to investigate the role of TGF-β/Smad3 signaling in palatal...

  • Effect of dopamine on the healing of acetic acid-induced gastric ulcers in rats. Nishikawa, K.; Amagase, K.; Takeuchi, K. // Inflammopharmacology;Oct2007, Vol. 15 Issue 5, p209 

    Dopamine, as a neurotransmitter in the brain, is also present in the gastroduodenal mucosa and has been implicated in several functions in these tissues. Recent study showed that dopamine acts as a potent antitumor/angiogenic activity through suppression of growth factor expression. Since growth...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics