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Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Severi, C. Sferra, R. Scirocco, A. Vetuschi, A. Pallotta, N. Pronio, A. Caronna, R. Di Rocco, G. Gaudio, E. Corazziari, E. Onori, P.
Description	Author Affiliation: Severi C ( La Sapienza University of Rome. carola.severi@uniroma1.it.)
Abstract	Mesenchymal cells transdifferentiation and extracellular matrix deposition are involved in the fibrotic process of Crohn's disease (CD). Mesenchymal smooth muscle cells (SMCs) de-differentiation, driven by Platelet-derived growth factor (PDGF) that counteracts Transforming growth factor (TGF-ß) has been studied in vascular muscle. The role of SMCs in intestinal fibrogenesis is still not clearly elucidated. Aim of the study was to evaluate the possible myogenic contribution to CD fibrotic process through the comparative analysis of histological, morphometric and molecular alterations occurring in human smooth muscle. Full thickness specimens were obtained from CD (non-involved and stenotic tracts) and healthy (control) ileum. Tissues were processed for histological and immunohistochemical (IHC) analyses and SMCs were isolated from the muscularis propria for morphofunctional and molecular (qPCR) analyses. CD stenotic ileum showed a significant increased thickness of all layers compared to CD non-involved and control ileum. IHC revealed an overexpression of -smooth muscle actin and collagens I-III throughout all intestinal layers only in stenotic tracts. The two growth factors, PDGF and TGF-ß, showed a progressive increase in expression in the muscle layer from CD non-involved to stenotic tracts. Freshly isolated SMCs presented alterations in CD non-involved tracts that progressively increased in the stenotic tracts consisting in a statistical increase in mRNA encoding for PDGF-ß and collagen III, paralleled to a decrease in TGF-ß and Tribbles-like protein-3 mRNA, and altered morphofunctional parameters consisting in progressive decreases in cell length and contraction to acetylcholine. These findings indicate that intrinsic myogenic alterations occur in CD ileum, that they likely precede stricture formation, and might represent suitable new targets for anti-fibrotic interventions.
File Format	HTM / HTML
ISSN	1121760X
e-ISSN	20388306
DOI	10.4081/ejh.2014.2457
Journal	European Journal of Histochemistry
Issue Number	4
Volume Number	58
Language	English
Publisher	PagePress
Publisher Date	2014-12-17
Publisher Place	Italy
Access Restriction	Open
Subject Keyword	Discipline Histocytochemistry Crohn Disease Ileum Muscle Proteins Metabolism Muscle, Smooth Actins Collagen Type Iii Constriction, Pathologic Pathology Proto-oncogene Proteins C-sis Transforming Growth Factor Beta Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Histology Biophysics

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