Syndecan-4 (Ryudocan) as a Defense Molecule in Endotoxin Shock
スポンサーリンク
概要
- 論文の詳細を見る
Syndecan-4(Ryudocan) is a transmembrane heparan sulfate proteoglycan, originally isolated as an antithrombin-binding molecule from the cloned rat microvascular endothelial cells. We have made syndecan-4 deficient mice by gene targeting to investigate the in vivo functions of syndecan-4, and found some interesting phenotypes, such as impairment of focal adhesion formation under restricted condition, severe thrombogenic tendency in the placental labyrinth, and susceptibility to k-carrageenan-induced obstructive nephropathy. As reviewed here, we have recently found that syndecan-4 deficient mice are more susceptible to endotoxin shock, leading to higher mortality than wild type mice. After intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4 deficient mice exhibited much higher mortality compared to wild type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were significantly lower in the deficient mice than in the wild types 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1β was higher in the deficient mice than in the wild type mice. It has been demonstrated that syndecan-4 expression in macrophages and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. On the other hand, transforming growth factor (TGF) -β1 dependent inhibition of LPS-induced IL-1β production was impaired in the syndecan-4 deficient macrophages. In addition, syndecan-4 deficiency impaired the TGF-β1 binding to macrophages, as well as the liver microvascular cells, leading to reduce inhibition of IL-Iβ production by TGF-2. Taken together, it is suggested that syndecan-4 is involved in prevention of endotoxin shock, at least partly through the inhibitory action of TGF-β1 on IL-1β production.
- 日本結合組織学会の論文
- 2002-09-25
著者
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Muramatsu Takashi
Department Of Biochemistry Nagoya University School Of Medicine
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Kojima Tetsuhito
First Department First Department Of Internal Medicine Nagoya University School Of Medicine:departme
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ISHIGURO Kazuhiro
Department of Biochemistry
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Ishiguro Kazuhiro
Department Of Biochemistry:first Department Of Internal Medicine Nagoya University School Of Medicin
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Muramatsu Takashi
Department Of Biochemistry
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MURAMATSU Takashi
Department of Animal Breeding and Reproduction, Faculty of Agriculture Utsunomiya University
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