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Subepithelial Myofibroblasts (subepithelial + myofibroblast)
Selected AbstractsDefective arachidonate release and PGE2 production in Gi,2-deficient intestinal and colonic subepithelial myofibroblastsINFLAMMATORY BOWEL DISEASES, Issue 3 2006Robert Andrew Edwards MD Abstract Background: Mice lacking the pertussis toxin-sensitive G-protein subunit Gi,2 spontaneously develop colitis and colon cancer. In the gut, arachidonate-derived prostaglandin E2 (PGE2) modulates intestinal immune responses and epithelial restitution and is derived largely from subepithelial myofibroblasts. Methods: We tested whether known decreases in arachidonate release in cells lacking Gi,2 would result in decreased PGE2 production and tissue PGE2 levels. PGE2 levels were significantly decreased in the colon of Gi,2,/, mice. Results: Gi,2,/, myofibroblasts from the small intestine and colon both released ,50% less arachidonate and 3- to 7-fold less PGE2 and 6-keto PGF1, in response to adenosine triphosphate, thrombin, tumor necrosis factor-,, or lipopolysaccharide, in a partially cyclooxygenase (COX)-2-dependent manner. Decreased arachidonate release did not appear to be caused by a defect in cPLA2 translocation in the absence of Gi,2. Basal myofibroblast COX-1 and COX-2 expression was downregulated in Gi,2,/, cells. No differences in proliferation rates were found between serum-starved or serum-activated wild-type (WT) and Gi,2,/, myofibroblasts. Finally, treatment of Gi,2,/, mice with the EP4 -specific PGE2 receptor agonist ONO-AE1-329 significantly decreased the severity of established colitis. Conclusions: These findings confirm a requirement for Gi,2 in intestinal and colonic myofibroblast-derived prostanoid production and confirm the importance of mucosal PGE2 in the suppression of colitis. [source] Mucosal remodeling in long-standing ulcerative colitis with colorectal neoplasia: Significant alterations of NCAM+ or ,-SMA+ subepithelial myofibroblasts and interstitial cellsPATHOLOGY INTERNATIONAL, Issue 10 2009Isao Okayasu Evidence has been provided in ulcerative colitis (UC) that early genomic instability of both epithelial and stromal cells is important for colorectal tumorigenesis, as well as remodeling and morphological alterations of mucosal crypts. To clarify roles of stromal cells in tumor development in UC, the present study focused on heterogeneous phenotypes of subepithelial myofibroblasts and interstitial cells, in association with mucosal remodeling. To clarify the relationship of alterations to tumorigenesis, mucosa of resected rectae from patients with UC (n= 49) and sporadic cancer (n= 10) were analyzed on immunohistochemistry and also on immunoelectron microscopy. Heterogeneous phenotypes of neural cell adhesion molecule (NCAM)+ and/or ,-smooth muscle actin (,-SMA)+ subepithelial myofibroblasts and interstitial cells were demonstrated, corresponding to colonic stellate cells. Decrease of NCAM+ subepithelial myofibroblasts and interstitial cells, and increase of ,-SMA+ interstitial cells were significant in UC with neoplasia as compared to without neoplasia. ,-SMA+ muscularis mucosae was significantly more thickened in tumor cases. Deposits of Masson's trichrome+ and type III and I collagen in the muscularis mucosae and lamina propria appeared to increase in relation to the numbers of ,-SMA+ interstitial cells. Mucosal remodeling with alterations of NCAM+ or ,-SMA+ subepithelial and interstitial cells may play a critical role in UC-associated tumorigenesis. [source] | ||||||||||