Cellular and molecular mechanisms of intestinal fibrosis

"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."