Fibrogenesis and fibrosis in inflammatory bowel diseases: Good and bad side of same coin?
Fibrogenesis in inflammatory bowel diseases is a complex phenomenon aimed at mucosal repair. However, it may provoke intestinal fibrosis with the development of strictures which require surgery. Therefore, fibrogenesis may be considered as a "two-faced" process when related to chronic intestinal inflammation. Many types of cells may be converted into the fibrogenic phenotype at different levels of the intestinal wall. A complex interaction of cytokines, adhesion molecules and growth factors is involved in the process. We report an overview of recent advances in molecular mechanisms of stricturizing Crohn's disease (CD) including the potential role of trasforming growth factor beta, protein kinase C and Ras, Raf and ERK proteins. Fibrotic growth factors such as vascular endothelial growth factor and platelet-derived growth factor, as well as the Endothelial-to-Mesenchymal Transition induced by transforming growth factor-β, are considered. Finally, our experience, focused on tumor necrosis factor α (the main cytokine of inflammatory bowel diseases) and the link between syndecan 1 (a heparan sulphate adhesion molecule) and basic fibroblast growth factor (a strong stimulator of collagen synthesis) is described. We hypothesize a possible molecular pattern for mucosal healing as well as how its deregulation could be involved in fibrotic complications of CD. A final clinical point is the importance of performing an accurate evaluation of the presence of fibrotic strictures before starting anti-tumor necrosis α treatment, which could worsen the lesions.
Mariabeatrice Principi, Floriana Giorgio, Giuseppe Losurdo, Viviana Neve, Antonella Contaldo, Alfredo Di Leo, Enzo Ierardi, Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
Mariabeatrice
M
Principi
Floriana
F
Giorgio
Giuseppe
G
Losurdo
Viviana
V
Neve
Antonella
A
Contaldo
Alfredo
A
Di Leo
Enzo
E
Ierardi
Basic fibroblast growth factor; Cellular fibrogenic phenotype; Fibrogenesis; Fibrosis; Inflammatory bowel diseases; Syndecan 1; Tumor necrosis factor -α