Are Interstitial Cells of Cajal Involved in Mechanical Stress-Induced Gene Expression and Impairment of Smooth Muscle Contractility in Bowel Obstruction?

Chester C. Wu, You Min Lin, Jerry Gao, John Winston, Leo K. Cheng, Xuan-Zheng Shi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background and Aims:The network of interstitial cells of Cajal (ICC) is altered in obstructive bowel disorders (OBD). However, whether alteration in ICC network is a cause or consequence of OBD remains unknown. This study tested the hypothesis that mechanical dilation in obstruction disrupts the ICC network and that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth muscle contractility in obstruction.Methods:Medical-grade silicon bands were wrapped around the distal colon to induce partial obstruction in wild-type and ICC deficient (W/Wv) mice.Results:In wild-type mice, colon obstruction led to time-dependent alterations of the ICC network in the proximal colon segment. Although unaffected on days 1 and 3, the ICC density decreased markedly and the network was disrupted on day 7 of obstruction. COX-2 expression increased, and circular muscle contractility decreased significantly in the segment proximal to obstruction. In W/Wv control mice, COX-2 mRNA level was 4.0 (±1.1)-fold higher (n=4) and circular muscle contractility was lower than in wild-type control mice. Obstruction further increased COX-2 mRNA level in W/Wv mice to 7.2 (±1.0)-fold vs. W/Wv controls [28.8 (±4.1)-fold vs. wild-type controls] on day 3. Obstruction further suppressed smooth muscle contractility in W/Wv mice. However, daily administration of COX-2 inhibitor NS-398 significantly improved muscle contractility in both W/Wv sham and obstruction mice.Conclusions:Lumen dilation disrupts the ICC network. ICC deficiency has limited effect on stretch-induced expression of COX-2 and suppression of smooth muscle contractility in obstruction. Rather, stretch-induced COX-2 plays a critical role in motility dysfunction in partial colon obstruction.

Original languageEnglish (US)
Article numbere76222
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 30 2013

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Interstitial Cells of Cajal
muscle strength
Mechanical Stress
mechanical stress
Gene expression
smooth muscle
Smooth Muscle
Muscle
prostaglandin synthase
Cells
Gene Expression
gene expression
mice
colon
Colon
cells
Muscles
Messenger RNA
Cyclooxygenase 2 Inhibitors
Dilatation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Are Interstitial Cells of Cajal Involved in Mechanical Stress-Induced Gene Expression and Impairment of Smooth Muscle Contractility in Bowel Obstruction? / Wu, Chester C.; Lin, You Min; Gao, Jerry; Winston, John; Cheng, Leo K.; Shi, Xuan-Zheng.

In: PLoS One, Vol. 8, No. 9, e76222, 30.09.2013.

Research output: Contribution to journalArticle

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abstract = "Background and Aims:The network of interstitial cells of Cajal (ICC) is altered in obstructive bowel disorders (OBD). However, whether alteration in ICC network is a cause or consequence of OBD remains unknown. This study tested the hypothesis that mechanical dilation in obstruction disrupts the ICC network and that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth muscle contractility in obstruction.Methods:Medical-grade silicon bands were wrapped around the distal colon to induce partial obstruction in wild-type and ICC deficient (W/Wv) mice.Results:In wild-type mice, colon obstruction led to time-dependent alterations of the ICC network in the proximal colon segment. Although unaffected on days 1 and 3, the ICC density decreased markedly and the network was disrupted on day 7 of obstruction. COX-2 expression increased, and circular muscle contractility decreased significantly in the segment proximal to obstruction. In W/Wv control mice, COX-2 mRNA level was 4.0 (±1.1)-fold higher (n=4) and circular muscle contractility was lower than in wild-type control mice. Obstruction further increased COX-2 mRNA level in W/Wv mice to 7.2 (±1.0)-fold vs. W/Wv controls [28.8 (±4.1)-fold vs. wild-type controls] on day 3. Obstruction further suppressed smooth muscle contractility in W/Wv mice. However, daily administration of COX-2 inhibitor NS-398 significantly improved muscle contractility in both W/Wv sham and obstruction mice.Conclusions:Lumen dilation disrupts the ICC network. ICC deficiency has limited effect on stretch-induced expression of COX-2 and suppression of smooth muscle contractility in obstruction. Rather, stretch-induced COX-2 plays a critical role in motility dysfunction in partial colon obstruction.",
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