Pathophysiology of motility dysfunction in bowel obstruction

Role of stretch-induced COX-2

Xuan-Zheng Shi, You Min Lin, Don W. Powell, Sushil K. Sarna

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In gastrointestinal conditions such as bowel obstruction, pseudo-obstruction, and idiopathic megacolon, the lumen of affected bowel segments is distended and its motility function impaired. Our hypothesis is that mechanical stretch of the distended segments alters gene expression of cyclooxygenase-2 (COX-2), which impairs motility function. Partial obstruction was induced with a silicon band in the distal colon of rats for up to 7 days, and wild-type and COX-2 gene-deficient mice for 4 days. Mechanical stretch was mimicked in vitro in colonic circular muscle strips and in primary culture of colonic circular smooth muscle cells (SMC) with a Flexercell system. The rat colonic circular muscle contractility was significantly decreased in the distended segment oral to obstruction, but not in the aboral segment. This change started as early as day 1 and persisted for at least 7 days after obstruction. The expression of COX-2 mRNA and protein increased dramatically also in the oral, but not aboral, segment. The upregulation of COX-2 expression started at 12 h and the effect persisted for 7 days. At 24 h after obstruction, the COX-2 mRNA level in the oral segment increased 26-fold compared with controls. This was not accompanied by any significant increase of myeloperoxidase or inflammatory cytokines. Immunohistochemical studies showed that COX-2 was selectively induced in the colonic SMC. In vitro stretch of colonic muscle strips or cultured SMC drastically induced COX-2 expression. Incubation of circular muscle strips from obstructed segment with COX-2 inhibitor NS-398 restored the contractility. The impairment of muscle contractility in obstructed colon was attenuated in the COX-2 gene-deficient mice. In conclusion, mechanical stretch in obstruction induces marked expression of COX-2 in the colonic SMC, and stretch-induced COX-2 plays a critical role in the suppression of smooth muscle contractility in bowel obstruction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume300
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Cyclooxygenase 2
Smooth Muscle Myocytes
Muscles
Colon
Megacolon
Messenger RNA
Cyclooxygenase 2 Inhibitors
Silicon
Peroxidase
Genes
Smooth Muscle
Up-Regulation
Cytokines
Gene Expression

Keywords

  • Cyclooxygenase-2
  • Mechanotranscription
  • Prostaglandins
  • Pseudo-obstruction
  • Smooth muscle

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Pathophysiology of motility dysfunction in bowel obstruction : Role of stretch-induced COX-2. / Shi, Xuan-Zheng; Lin, You Min; Powell, Don W.; Sarna, Sushil K.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 300, No. 1, 01.2011.

Research output: Contribution to journalArticle

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