Fibrogenesis in Crohn's disease.
BACKGROUND
Over one-third of patients with Crohn's disease (CD) will develop an intestinal stricture and the great majority of these will require at least one surgical procedure. While the pathogenesis of inflammation in CD has been extensively investigated, knowledge of stricture pathogenesis remains limited. The aim of this review is to discuss the current understanding of fibrogenesis in CD and to outline potential directions in research and therapeutics.


METHODS
The electronic literature (January 1966 to May 2006) on CD-associated fibrosis was reviewed. Further references were obtained by cross-referencing from key articles.


RESULTS
CD-associated fibrosis results from chronic transmural inflammation and a complex interplay among intestinal mesenchymal cells, cytokines, and local inflammatory cells. The fibroblast is the key cell type mediating stricture formation. The cytoarchitecure of the bowel wall is altered with disruption of the muscularis mucosa, thickening of the muscularis propria, and deposition of collagen throughout. The cytokine TGF-beta appears critical in this process, acting to increase growth factor and extracellular matrix (ECM) production and dysregulate ECM turnover. Potential therapeutic interventions are likely to concentrate on modulating down-stream targets of TGF-beta.


CONCLUSIONS
Greater understanding of the biology of fibrostenosis is likely to yield significant advances in our ability to care for patients with stricturing CD. Potential dividends of this approach include identification of novel therapeutic targets and biomarkers useful for prognostication and therapeutic monitoring.
Burke
John P
JP
Department of Surgery, Mater Misericordiae University Hospital and UCD School of Medicine and Medical Sciences, Dublin, Ireland.
Mulsow
Jurgen J
JJ
O'Keane
Conor
C
Docherty
Neil G
NG
Watson
R William G
RW
O'Connell
P Ronan
PR
D003424:Crohn Disease / Q000150:complications / Q000473:pathology*; D018450:Disease Progression; D005355:Fibrosis / Q000150:complications / Q000473:pathology; D006801:Humans; D007415:Intestinal Obstruction / Q000209:etiology / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies