Myofibroblasts. II. Intestinal subepithelial myofibroblasts

Intestinal subepithelial myofibroblasts (ISEMF) and the interstitial cells of Cajal are the two types of myofibroblasts identified in the intestine. I ntestinal myofibroblasts are activated and proliferate in response to vario us growth factors, particularly the platelet-derived growth factor (PDGF) f amily, which includes PDGF-BB and stem cell factor (SCF), through expressio n of PDGF receptors and the SCF receptor c-hit. ISEMF have been shown to pl ay important roles in the organogenesis of the intestine, and growth factor s and cytokines secreted by these cells promote epithelial restitution and proliferation, i.e,, wound repair. Their role in the fibrosis of Crohn's di sease and collagenous colitis is being investigated. Through cyclooxygenase (COX)-1 and COX-2 activation, ISEMF augment intestinal ion secretion in re sponse to certain secretagogues. By forming a subepithelial barrier to Nadiffusion, they create a hypertonic compartment that may account for the ab ility of the gut to transport fluid against an adverse osmotic gradient. Th rough the paracrine secretion of prostaglandins and growth factors (e.g., t ransforming growth factor-beta), ISEMF may play a role in colonic tumorigen esis and metastasis. COX-2 in polyp ISEMF may be a target for nonsteroidal anti-inflammatory drugs (NSAIDs), which would account for the regression of the neoplasms in familial adenomatous polyposis and the preventive effect of NSAIDs in the development of sporadic colon neoplasms. More investigatio n is needed to clarify the functions of these pleiotropic cells.