Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease

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...

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Bibliographic Details
Published in:PloS one 2013-02, Vol.8 (2), p.e57023-e57023
Main Authors: Mattii, Letizia, Ippolito, Chiara, Segnani, Cristina, Battolla, Barbara, Colucci, Rocchina, Dolfi, Amelio, Bassotti, Gabrio, Blandizzi, Corrado, Bernardini, Nunzia
Format: Article
Language:English
Subjects:
Abnormalities
Adult
Aged
Aged, 80 and over
Analysis
Biology
Cancer
Care and treatment
Colon
Colon - metabolism
Colon - pathology
Connexin 26
Connexin 43
Connexin 43 - genetics
Connexin 43 - metabolism
Connexins - genetics
Connexins - metabolism
Diet
Diverticulum, Colon - genetics
Diverticulum, Colon - metabolism
Diverticulum, Colon - pathology
Female
Gap junctions
Gastrointestinal diseases
Gene Expression Profiling
Genetic factors
Habits
Histology
Humans
Image analysis
Image processing
Immunohistochemistry
Inflammation
Intestine
Kinases
Lesions
Localization
Male
Medical research
Medicine
Middle Aged
Motility
Muscle contraction
Muscle, Smooth - metabolism
Muscle, Smooth - pathology
Muscles
Nervous system
Pathogenesis
Patients
Phosphorylation
Protein kinase C
Protein Kinase C - genetics
Protein Kinase C - metabolism
Proteins
Proto-Oncogene Proteins c-kit - genetics
Proto-Oncogene Proteins c-kit - metabolism
Quantitative analysis
rhoA GTP-Binding Protein - genetics
rhoA GTP-Binding Protein - metabolism
RhoA protein
Rodents
Smooth muscle
Studies
Tissues
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0057023