Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis

  • C. Severi La Sapienza University of Rome, Italy.
  • R. Sferra University of L'Aquila, Italy.
  • A. Scirocco La Sapienza University of Rome, Italy.
  • A. Vetuschi University of L'Aquila, Italy.
  • N. Pallotta La Sapienza University of Rome, Italy.
  • A. Pronio La Sapienza University of Rome, Italy.
  • R. Caronna La Sapienza University of Rome, Italy.
  • G. Di Rocco La Sapienza University of Rome, Italy.
  • E. Gaudio La Sapienza University of Rome, Italy.
  • E. Corazziari La Sapienza University of Rome, Italy.
  • P. Onori | paolo.onori@uniroma1.it La Sapienza University of Rome, Italy.

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-β) 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 α-smooth muscle actin and collagens I-III throughout all intestinal layers only in stenotic tracts. The two growth factors, PDGF and TGF-β, 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-β and collagen III, paralleled to a decrease in TGF-β 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.

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Author Biographies

C. Severi, La Sapienza University of Rome
Department of Internal Medicine and Medical Specialties
R. Sferra, University of L'Aquila
Department of Biotechnological and Applied Clinical Sciences
A. Scirocco, La Sapienza University of Rome
Department of Internal Medicine and Medical Specialties
A. Vetuschi, University of L'Aquila
Department of Biotechnological and Applied Clinical Sciences
N. Pallotta, La Sapienza University of Rome
Department of Internal Medicine and Medical Specialties
A. Pronio, La Sapienza University of Rome
Departmentof General Surgery "P. Stefanini"
R. Caronna, La Sapienza University of Rome
Section of Multidisciplinary Surgery “F. Duranteâ€
G. Di Rocco, La Sapienza University of Rome
Department of Surgical Sciences
E. Gaudio, La Sapienza University of Rome
Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences
E. Corazziari, La Sapienza University of Rome
Department of Internal Medicine and Medical Specialties
P. Onori, La Sapienza University of Rome
Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences
Published
2014-12-17
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Section
Original Papers
Supporting Agencies
Italian Ministry of Education, University and Research (PRIN 2009, B81J11002260001) to CS
Keywords:
Fibrosis, Crohn’s disease, ileal smooth muscle cells, stricture formation, PDGF, TGF-β.
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How to Cite
Severi, C., Sferra, R., Scirocco, A., Vetuschi, A., Pallotta, N., Pronio, A., Caronna, R., Di Rocco, G., Gaudio, E., Corazziari, E., & Onori, P. (2014). Contribution of intestinal smooth muscle to Crohn’s disease fibrogenesis. European Journal of Histochemistry, 58(4). https://doi.org/10.4081/ejh.2014.2457