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Regulation of SRF/CArG‐dependent gene transcription during chronic partial obstruction of murine small intestine

Publication ,  Journal Article
Chen, J; Chen, H; Sanders, KM; Perrino, BA
Published in: Neurogastroenterology & Motility
July 2008

Intestinal obstructions lead to a variety of motility disorders. Small intestine smooth muscles undergo dramatic phenotypic changes in response to obstruction, but the underlying molecular mechanisms are unknown. Using RT‐PCR, ChIP, Re‐ChIP, and Western blots, we examined the effect of small bowel mechanical obstruction on smooth muscle gene expression. Obstruction caused a transient hyperplasia, followed by a prolonged hypertrophic response of small intestine smooth muscle cells. Smooth muscle myosin heavy chain (MHC), α‐actin, and γ‐actin expression decreased initially, and then increased as hypertrophy developed. Myocardin expression decreased initially and then increased, while kruppel‐like factors (KLF)4 and KLF5 expression increased initially, and then decreased. Serum response factor (SRF) expression decreased initially, and then recovered to sham‐operated levels as hypertrophy developed. SRF binding to smooth muscle MHC and α‐actin promoters decreased initially, but then increased above sham‐operated levels as hypertrophy developed. Elk‐1 binding to smooth muscle myosin heavy chain and α‐actin promoters increased initially, and then decreased to sham‐operated levels as hypertrophy developed. c‐fos expression increased initially, which was associated with increased SRF/Elk‐1 binding to the c‐fos promoter. The Elk‐1 phosphorylation inhibitor U‐0126 inhibited the increase in c‐fos expression. These findings indicate a dynamic response of small intestine smooth muscles to bowel obstruction involving switching between differentiated, proliferative, and hypertrophic phenotypes. These results suggest that changes in the expression and interactions between SRF, myocardin, Elk‐1, and c‐fos play key roles in the phenotypic switching of small intestine smooth muscles in response to mechanical obstruction.

Duke Scholars

Published In

Neurogastroenterology & Motility

DOI

EISSN

1365-2982

ISSN

1350-1925

Publication Date

July 2008

Volume

20

Issue

7

Start / End Page

829 / 842

Publisher

Wiley

Related Subject Headings

  • Gastroenterology & Hepatology
  • 1116 Medical Physiology
  • 1109 Neurosciences
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, J., Chen, H., Sanders, K. M., & Perrino, B. A. (2008). Regulation of SRF/CArG‐dependent gene transcription during chronic partial obstruction of murine small intestine. Neurogastroenterology & Motility, 20(7), 829–842. https://doi.org/10.1111/j.1365-2982.2008.01149.x
Chen, J., H. Chen, K. M. Sanders, and B. A. Perrino. “Regulation of SRF/CArG‐dependent gene transcription during chronic partial obstruction of murine small intestine.” Neurogastroenterology & Motility 20, no. 7 (July 2008): 829–42. https://doi.org/10.1111/j.1365-2982.2008.01149.x.
Chen J, Chen H, Sanders KM, Perrino BA. Regulation of SRF/CArG‐dependent gene transcription during chronic partial obstruction of murine small intestine. Neurogastroenterology & Motility. 2008 Jul;20(7):829–42.
Chen, J., et al. “Regulation of SRF/CArG‐dependent gene transcription during chronic partial obstruction of murine small intestine.” Neurogastroenterology & Motility, vol. 20, no. 7, Wiley, July 2008, pp. 829–42. Crossref, doi:10.1111/j.1365-2982.2008.01149.x.
Chen J, Chen H, Sanders KM, Perrino BA. Regulation of SRF/CArG‐dependent gene transcription during chronic partial obstruction of murine small intestine. Neurogastroenterology & Motility. Wiley; 2008 Jul;20(7):829–842.
Journal cover image

Published In

Neurogastroenterology & Motility

DOI

EISSN

1365-2982

ISSN

1350-1925

Publication Date

July 2008

Volume

20

Issue

7

Start / End Page

829 / 842

Publisher

Wiley

Related Subject Headings

  • Gastroenterology & Hepatology
  • 1116 Medical Physiology
  • 1109 Neurosciences
  • 1103 Clinical Sciences