Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease

Gastroenterology and Hepatology Section, Department of Clinical and Experimental Medicine, University of Perugia, Via Enrico Dal Pozzo, Padiglione W., 06100 Perugia, Italy.
Journal of Clinical Pathology (Impact Factor: 2.92). 10/2005; 58(9):973-7. DOI: 10.1136/jcp.2005.026112
Source: PubMed


Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis.
To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis.
Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls.
Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively.
Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041).
Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.

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Available from: Graziella Bellone, Feb 10, 2014
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    • "Notably, DD has been associated also with neuromuscular dysfunctions (Bassotti et al., 2001; Bassotti and Villanacci, 2012). Colonic motor abnormalities in DD have been hypothesized to result from changes in enteric nerves, smooth muscle functions (Golder et al., 2003; Bassotti et al., 2005a; Mattii et al., 2013), and low-grade mucosal and myenteric inflammation (Bassotti et al., 2013). In addition, alterations in the excitatory control by enteric cholinergic nerves have been observed in DD, but not by all groups (Tomita et al., 2000; Golder et al., 2003). "
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    ABSTRACT: Background and purpose: The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). Experimental approach: Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. Key results: In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. Conclusions and implications: In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity.
    Full-text · Article · Apr 2014 · British Journal of Pharmacology
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    • "These cells function primarily as pacemakers, but they can also act as cellular bridges connecting nerve varicosities with several SMCs, thus ensuring a proper diffusion of contractile inputs throughout the tunica muscularis [45]. In this respect, the analysis of neuromuscular ICC density, as performed in the present study, highlighted a significant decrease in the density of these cells throughout the whole tunica muscularis of DD patients, at level of both CM and LM layers, in agreement with previous results reported by Bassotti et al. [7]. Of note, patients with DD have been shown to display an increase in both overall and rhythmic colonic contractions [2], [46]. "
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    ABSTRACT: The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.
    Full-text · Article · Feb 2013 · PLoS ONE
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    Full-text · Article · Sep 1994 · The American Journal of Gastroenterology
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