title: Cellular and molecular mechanisms of intestinal fibrosis.
abstract: Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelial- and endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic process, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine and Public Health, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Speca
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giusti
authors.forename: Florian
authors.initials: F
authors.lastname: Rieder
authors.forename: Giovanni
authors.initials: G
authors.lastname: Latella
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005762:Gastroenterology / Q000379:methods / Q000592:standards*; D017408:Guidelines as Topic; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism; D007410:Intestinal Diseases / Q000235:genetics* / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology; D018384:Oxidative Stress; D015291:Transforming Growth Factors / Q000378:metabolism; D014945:Wound Healing
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D015291:Transforming Growth Factors