| Co-Investigator(Kenkyū-buntansha) |
KAIBORI Masaki Kansai Medical University, Faculty of medicine, Instructor, 医学部, 助手 (30333199)
SATOI Sohei Kansai Medical University, Faculty of medicine, Instructor, 医学部, 助手 (90340695)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Plasma fibronectin (Fn) has a broad range of biological functions involved in cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, reticuloendothelial system function, and ischemic injury. In this study, we examined the effects of Fn on endotoxin-induced liver injury after partial hepatectomy, D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant liver failure in mice, burned wound sepsis caused by methicillin resistance Staphylococcus aureus (MRSA) and incisional wound healing in a rat skin incision and celiotomy. Fn prevented endotoxin-induced liver injury after partial hepatectomy, at least in part through the inhibition of production of inflammatory cytokines, necrosis and apoptosis in the remaining liver. Moreover, Fn protected against GalN/LPSinduced liver failure by a mechanism involving inhibition of nuclear factor-kB activation, which caused down-regulation of tumor necrosis factor-a and involved up-regulation of interleukin-10, and elevation of Bcl-xL induced a blockage of apoptotic signals. Secondly, Fn prevented burned wound sepsis caused by MRSA via significant enhancement of macrophage phagocytosis. Finally, a single injection of Fn significantly increased the breaking strength of the skin and the bursting pressure of the abdominal wall. The amount of hydroxyproline in the skin incisional wound with pFn was significantly higher than with an injection of albumin as control. In rats in whom Fn levels were decreased by anti-rat Fn serum, a single administration of Fn significantly increased the breaking strength of the skin and the bursting pressure of the abdominal wall, compared to a control injection of albumin.
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