Abstract
Background and AimsThe 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.MethodsMedical-grade silicon bands were wrapped around the distal colon to induce partial obstruction in wild-type and ICC deficient (W/Wv) mice.ResultsIn 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.ConclusionsLumen 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.
Highlights
Bowel obstruction, acute or chronic, is a significant health challenge
We found in a rat model of partial colon obstruction that lumen distention proximal to obstruction markedly induces expression of mechanosensitive genes such as that encoding cyclooxygenase-2 (COX-2) [5,6,7,8] selectively in smooth muscle cells (SMC)
We determined the effect of lumen dilation on the interstitial cells of Cajal (ICC) network (ICC-MY) in the mouse model of partial colon obstruction
Summary
Acute or chronic, is a significant health challenge. It may be caused by a physical blockade of the lumen (mechanical obstruction), or present as lumen dilation without an organic obstruction (functional obstruction) [1,2,3]. Mechanical stress-induced COX-2, through derived prostaglandins (PGs) PGE2, plays a critical role in the suppression of smooth muscle contractility in obstruction [5,6]. The network of interstitial cells of Cajal (ICC) is altered in obstructive bowel disorders (OBD). 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. COX-2 expression increased, and circular muscle contractility decreased significantly in the segment proximal to obstruction. ICC deficiency has limited effect on stretch-induced expression of COX-2 and suppression of smooth muscle contractility in obstruction. Stretch-induced COX-2 plays a critical role in motility dysfunction in partial colon obstruction
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