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University of Texas Medical Branch at Galveston, Departments of Internal Medicine, Physiology, and Biophysics and Pathology, Galveston, Texas 77555-0567
Intestinal
subepithelial myofibroblasts (ISEMF) and the interstitial cells of
Cajal are the two types of myofibroblasts identified in the intestine.
Intestinal myofibroblasts are activated and proliferate in response to
various growth factors, particularly the platelet-derived growth factor
(PDGF) family, which includes PDGF-BB and stem cell factor (SCF),
through expression of PDGF receptors and the SCF receptor
c-kit. ISEMF have been shown to play
important roles in the organogenesis of the intestine, and growth
factors and cytokines secreted by these cells promote epithelial restitution and proliferation, i.e., wound repair. Their role in the
fibrosis of Crohn's disease and collagenous colitis is being
investigated. Through cyclooxygenase (COX)-1 and COX-2 activation, ISEMF augment intestinal ion secretion in response to certain secretagogues. By forming a subepithelial barrier to
Na+ diffusion, they create a
hypertonic compartment that may account for the ability of the gut to
transport fluid against an adverse osmotic gradient. Through the
paracrine secretion of prostaglandins and growth factors (e.g.,
transforming growth factor-
), ISEMF may play a role in
colonic tumorigenesis 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 investigation is
needed to clarify the functions of these pleiotropic cells.
interstitial cells of Cajal; cyclooxygenase; chemoprevention; wound repair; fibrosis; electrolyte transport; immunophysiology
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