Pathogenic aspects and therapeutic avenues of intestinal fibrosis in Crohn's disease.
In Crohn's disease, one of the two major forms of inflammatory bowel diseases in human beings, persistent and chronic inflammation promotes fibrotic processes thereby facilitating formation of strictures, the most common indication for surgical intervention in this disorder. The pathogenesis of Crohn's disease-associated fibrosis is not fully understood, but variants of genes involved in the recognition of microbial components/products [e.g. CARD15 (caspase-activating recruitment domain 15) and ATG16L1 (autophagy-related 16-like 1)] are associated with this phenotype, and experimental evidence suggests that intestinal fibrosis results from an altered balance between deposition of ECM (extracellular matrix) and degradation of ECM by proteases. Studies have also contributed to identify the main phenotypic and functional alterations of cells involved in the fibrogenic process, as well as molecules that stimulate such cells to produce elevated amounts of collagen and other ECM-related proteins. In the present review, we assess the current knowledge about cellular and molecular mediators of intestinal fibrosis and describe results of recent studies aimed at testing the preventive/therapeutic effect of compounds in experimental models of intestinal fibrosis.
Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
Francesca
F
Zorzi
Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
Emma
E
Calabrese
Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy Gi.monteleone@med.uniroma2.it.
Giovanni
G
Monteleone
D000818:Animals; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D005765:Gastrointestinal Agents / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D058990:Molecular Targeted Therapy; D010641:Phenotype; D012307:Risk Factors; D015398:Signal Transduction
D005765:Gastrointestinal Agents
Crohn's disease; Smad; TGF-β1; collagen; extracellular matrix