Syndecan-4 as a molecule involved in defense mechanisms.
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.
Ishiguro
Kazuhiro
K
Department of Biochemistry and Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Kojima
Tetsuhito
T
Muramatsu
Takashi
T
D000818:Animals; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology; D053671:Syndecan-4; D016212:Transforming Growth Factor beta / Q000502:physiology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016212:Transforming Growth Factor beta