Ishiguro Kazuhiro, Kojima Tetsuhito, Muramatsu Takashi
Department of Biochemistry and Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Glycoconj J. 2002 May-Jun;19(4-5):315-8. doi: 10.1023/A:1025308702966.
Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Syndecan-4-deficient [(Synd4(-/-)] mice were produced to clarify the in vivo role of syndecan-4. Synd4(-/-) mice were more susceptible to kappa-carrageenan-induced nephropathy, and the placental labyrinth from the deficient embryos exhibited more thrombi than wild-type ones. Importantly, Synd4(-/-) mice were more susceptible to endotoxin shock. Further analysis revealed that the mechanism to suppress excessive production of interleukin-1beta (1L-1beta) by transforming growth factor-beta (TGF-beta) was impaired in the deficient mice. TGF-beta, one of the cytokines involved in the suppression mechanism, bound to heparan sulfate chain of syndecan-4, which was induced in macrophages and the microvasculature after administration of lipopolysaccharide. Therefore, augmentation of TGF-beta function by induced syndecan-4 was suggested as a mechanism of the suppressive action of syndecan-4 against endotoxin shock.
Syndecan-4是一种属于syndecan家族的跨膜硫酸乙酰肝素蛋白聚糖。为阐明syndecan-4在体内的作用，制备了syndecan-4基因敲除（Synd4(-/-)）小鼠。Synd4(-/-)小鼠对κ-角叉菜胶诱导的肾病更易感，且来自缺陷胚胎的胎盘迷路比野生型的有更多血栓。重要的是，Synd4(-/-)小鼠对内毒素休克更易感。进一步分析表明，在缺陷小鼠中，转化生长因子-β（TGF-β）抑制白细胞介素-1β（IL-1β）过度产生的机制受损。TGF-β是参与该抑制机制的细胞因子之一，与syndecan-4的硫酸乙酰肝素链结合，syndecan-4在给予脂多糖后在巨噬细胞和微血管中被诱导产生。因此，诱导syndecan-4增强TGF-β功能被认为是syndecan-4对内毒素休克发挥抑制作用的机制。
