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Published in: Irish Journal of Medical Science (1971 -) 4/2018

01-11-2018 | Review Article

Prof Ronan O’Connell Festschrift: Stricture pathogenesis in Crohn’s disease—the role of intestinal fibroblasts

Author: Jürgen Mulsow

Published in: Irish Journal of Medical Science (1971 -) | Issue 4/2018

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Abstract

Approximately one-third of patients with Crohn’s disease have a distinct fibrostenosing phenotype predisposing them to recurrent intestinal stricture formation. The intestinal fibroblast was thought to play a critical role in the abnormal wound healing which ends in stricture formation. Recognising this, a laboratory-based research study was initiated at the Mater Misericordiae Hospital and University College Dublin with the aim of investigating the key steps in intestinal fibroblast-mediated stricture pathogenesis. An in vitro model was developed using cultured fibroblasts taken from sites of stricture in patients undergoing surgery. In summary, these fibroblasts were shown to carry multiple distinct pro-fibrotic phenotypic changes which may explain the abnormal wound healing and scar formation found at their sites of origin. This paper reviews that body of work, undertaken by series of surgical researchers and scientists, and driven by the insight, guidance and mentorship of Professor Ronan O’Connell.
Literature
1.
go back to reference Beddy DJ, Watson WR, Fitzpatrick JM, O’Connell PR (2004) Critical involvement of stress-activated mitogen-activated protein kinases in the regulation of intracellular adhesion molecule-1 in serosal fibroblasts isolated from patients with Crohn's disease. J Am Coll Surg 199(2):234–242CrossRefPubMed Beddy DJ, Watson WR, Fitzpatrick JM, O’Connell PR (2004) Critical involvement of stress-activated mitogen-activated protein kinases in the regulation of intracellular adhesion molecule-1 in serosal fibroblasts isolated from patients with Crohn's disease. J Am Coll Surg 199(2):234–242CrossRefPubMed
2.
go back to reference Brannigan AE, Watson RW, Beddy D, Hurley H, Fitzpatrick JM, O’Connell PR (2002) Increased adhesion molecule expression in serosal fibroblasts isolated from patients with inflammatory bowel disease is secondary to inflammation. Ann Surg 235(4):507–511CrossRefPubMedPubMedCentral Brannigan AE, Watson RW, Beddy D, Hurley H, Fitzpatrick JM, O’Connell PR (2002) Increased adhesion molecule expression in serosal fibroblasts isolated from patients with inflammatory bowel disease is secondary to inflammation. Ann Surg 235(4):507–511CrossRefPubMedPubMedCentral
3.
go back to reference Beddy D, Watson RW, Fitzpatrick JM, O’Connell PR (2004) Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn’s disease. Br J Surg 91(1):72–77CrossRefPubMed Beddy D, Watson RW, Fitzpatrick JM, O’Connell PR (2004) Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn’s disease. Br J Surg 91(1):72–77CrossRefPubMed
4.
go back to reference Beddy D, Mulsow J, Watson RW, Fitzpatrick JM, O’Connell PR (2006) Expression and regulation of connective tissue growth factor by transforming growth factor beta and tumour necrosis factor alpha in fibroblasts isolated from strictures in patients with Crohn’s disease. Br J Surg 93(10):1290–1296CrossRefPubMed Beddy D, Mulsow J, Watson RW, Fitzpatrick JM, O’Connell PR (2006) Expression and regulation of connective tissue growth factor by transforming growth factor beta and tumour necrosis factor alpha in fibroblasts isolated from strictures in patients with Crohn’s disease. Br J Surg 93(10):1290–1296CrossRefPubMed
5.
go back to reference Mulsow JJ, Watson RW, Fitzpatrick JM, O’Connell PR (2005) Transforming growth factor-beta promotes pro-fibrotic behavior by serosal fibroblasts via PKC and ERK1/2 mitogen activated protein kinase cell signaling. Ann Surg 242(6):880–887 discussion 7-9CrossRefPubMedPubMedCentral Mulsow JJ, Watson RW, Fitzpatrick JM, O’Connell PR (2005) Transforming growth factor-beta promotes pro-fibrotic behavior by serosal fibroblasts via PKC and ERK1/2 mitogen activated protein kinase cell signaling. Ann Surg 242(6):880–887 discussion 7-9CrossRefPubMedPubMedCentral
6.
go back to reference Regan MC, Flavin BM, Fitzpatrick JM, O’Connell PR (2000) Stricture formation in Crohn’s disease: the role of intestinal fibroblasts. Ann Surg 231(1):46–50CrossRefPubMedPubMedCentral Regan MC, Flavin BM, Fitzpatrick JM, O’Connell PR (2000) Stricture formation in Crohn’s disease: the role of intestinal fibroblasts. Ann Surg 231(1):46–50CrossRefPubMedPubMedCentral
7.
go back to reference Burke JP, Watson RW, Mulsow JJ, Docherty NG, Coffey JC, O’Connell PR (2010) Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts. Br J Surg 97(6):892–901CrossRefPubMed Burke JP, Watson RW, Mulsow JJ, Docherty NG, Coffey JC, O’Connell PR (2010) Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts. Br J Surg 97(6):892–901CrossRefPubMed
Metadata
Title
Prof Ronan O’Connell Festschrift: Stricture pathogenesis in Crohn’s disease—the role of intestinal fibroblasts
Author
Jürgen Mulsow
Publication date
01-11-2018
Publisher
Springer London
Published in
Irish Journal of Medical Science (1971 -) / Issue 4/2018
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-018-1850-x

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