Are interstitial cells of Cajal involved in mechanical stress-induced gene expression and impairment of smooth muscle contractility in bowel obstruction?

Wu CC, Lin YM, Gao J, Winston JH, Cheng LK, Shi XZ
PLoS One. 2013 8 (9): e76222

PMID: 24098782 · PMCID: PMC3786942 · DOI:10.1371/journal.pone.0076222

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/W(v)) 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/W(v) 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/W(v) mice to 7.2 (±1.0)-fold vs. W/W(v) controls [28.8 (±4.1)-fold vs. wild-type controls] on day 3. Obstruction further suppressed smooth muscle contractility in W/W(v) mice. However, daily administration of COX-2 inhibitor NS-398 significantly improved muscle contractility in both W/W(v) 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.

MeSH Terms (14)

Animals Blotting, Western Cyclooxygenase 2 Cyclooxygenase Inhibitors Fluorescent Antibody Technique Gene Expression Regulation Interstitial Cells of Cajal Intestinal Obstruction Mice Muscle, Smooth Muscle Contraction Nitrobenzenes Real-Time Polymerase Chain Reaction Sulfonamides

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