Myofibroblasts. II. Intestinal subepithelial myofibroblasts

Abstract

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-β), 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.

Subepithelial myofibroblast in lung adenocarcinoma: a histological indicator of excellent prognosis

“…[29][30][31][32] In fact, the features of subepithelial myofibroblasts in lung adenocarcinoma are quite similar to those reported for pericryptal fibroblasts Figure 4 Subepithelial myofibroblasts in invasive lung adenocarcinomas (a-smooth muscle actin staining). In areas of central collapse and fibrosis, the myofibroblastic layer around the neoplastic acinar structure was discontinuous (a).…”

“…Pericryptal fibroblasts are more abundant in adenoma than in normal colon, and gradually decrease during the progression from adenoma to intramucosal carcinoma to submucosal invasive carcinoma. [29][30][31][32] In invasive carcinomas they are virtually absent. 29 Pericryptal fibroblasts are also absent in normal gastric mucosa.…”

“…[29][30][31][32] In invasive carcinomas they are virtually absent. 29 Pericryptal fibroblasts are also absent in normal gastric mucosa. 33 Interestingly, however, they appear in intestinal metaplastic glands, but disappear in the neoplastic glands of gastric adenocarcinomas of intestinal type.…”

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

“…34 Additionally, CB2 knockout mice are more sensitive than wild-type littermates to bleomycin-induced dermal fibrosis. 35 As > 30 % of patients with Crohn ' s disease develop intestinal fibrosis leading to stricture formation, frequently requiring surgical resection, 36 and myofibroblasts are key cells in the process of wound healing and stricture formation in the gut, 37 we investigated the in vitro effects of MAEA on myofibroblasts isolated from intestinal Crohn ' s disease strictures. We found that MAEA reduced collagen production by strictured Crohn ' s disease myofibroblasts and increased their migration ability, thus supporting the view that endocannabinoid pathways might be involved in the fibrogenic process in Crohn ' s disease.…”

Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass

“…1,6,17,18 CAFs as key factors of abnormal epithelial-stromal interaction and their powerful tumor-supportive effect (eg, increased regulator ligand and extracellular matrix molecule expression) are well known compared with normal stromal cells with similar morphology, that is, subepithelial myofibroblasts. [18][19][20] Tumor cellreleased exosomes are also detectable in the circulation where the plasma level of their specific proteins (eg, CD63 and tumor susceptibility gene 101/TSG101) and miRNA content may be useful as diagnostic and/or prognostic markers in different tumor types including colorectal carcinomas. [21][22][23][24] Our study was designed to analyze the top exosome-specific markers based on change of their tissue mRNA level during colorectal adenomacarcinoma sequence.…”