| Co-Investigator(Kenkyū-buntansha) |
MORITA Makoto Dpt of Surgery II,Kyushu University, Stuff, 医学部, 医員
津川 康治 九州大学, 医学部, 医員
MIGOH Shinichiro Dpt of Surgery II,Kyushu University, Stuff, 医学部, 医員
OHTA Msayuki Dpt of Surgery II,Kyushu University, Stuff, 医学部, :医員
TANOUE Kazuo Dpt of Surgery II,Kyushu University, Stuff, 医学部, 助手
TSUGAWA Kouji Dpt of Surgery II,Kyushu University, Stuff
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| Research Abstract |
The lower esophagus is predisposed to variceal development and rupture in the portal hypertensive (PHT) state. The esophageal muscularis mucosae and epithelium overlying large submucosal veins in PHT rats, produced by staged portal vein ligation, were significantly thinner than in controls. Extracellular matrix (ECM), which is one of the key factors in cellular and tissue structural support. In immunostaining study, fibronectin (FN) and laminin (LM) in muscularis mucosae was significantly increased, and fibronectin receptor (FNR) was significantly decreased in PHT than in controls. Basic fibroblast growth factor (bFGF) enhances cell migration, proliferation, and tissue integrity. The immunostaining intensity of bFGF and FGFR-2 in muscularis mucosa of lower esophagus was significantly reduced in PHT rats. Basic FGF and FGFR-2 mRNAs expressions in PHT esophageal mucosa were significantly reduced vs controls by 30.8% and 30.3%. We postulated that overexpression of nitric oxide (NO) synthase at this site may produce a local hyperdynamic state and varices which would alter the mucosa structurally. With immunofluorescence staining, intensities of c-NOS and i-NOS in the endothelia of submucosal veins were also higher in PHT rats than in controls. c-NOS mRNAs expressions in PHT esophageal mucosa were significantly increased than controls.
Since the spatial organization of fibronectin receptors affects the strength and structural integrity of the ECM, and bFGF stimulates smooth muscle cell proliferation and their growth, our findings of ECM, bFGF and NOS abnormalities in PHT esophagus, combined with its epithelial and muscularis mucosae thinness, suggest a mechanism by which varices may be predisposed to rupture in the esophagus.
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