title: Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-β1and Downregulates Syndecan-4 in Cultured Vascular Endothelial Cells.
abstract: Proteoglycans are macromolecules that consist of a core protein and one or more glycosaminoglycan side chains. A small leucine-rich dermatan sulfate proteoglycan, biglycan, is one of the predominant types of proteoglycans synthesized by vascular endothelial cells; however, the physiological functions of biglycan are not completely understood. In the present study, bovine aortic endothelial cells in culture were transfected with small interfering RNAs for biglycan, and the expression of other proteoglycans was examined. Transforming growth factor-β1signaling was also investigated, because the interaction of biglycan with cytokines has been reported. Biglycan was found to form a complex with either transforming growth factor-β1or the transforming growth factor-β1type I receptor, ALK5, and to intensify the phosphorylation of Smad2/3, resulting in a lower expression of the transmembrane heparan sulfate proteoglycan, syndecan-4. This is the first report to clarify the function of biglycan as a regulatory molecule of the ALK5-Smad2/3 TGF-β1signaling pathway that mediates the suppression of syndecan-4 expression in vascular endothelial cells. J. Cell. Biochem. 118: 1087-1096, 2017. © 2016 Wiley Periodicals, Inc.
authors: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
authors: Takato
authors: T
authors: Hara
authors: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
authors: Eiko
authors: E
authors: Yoshida
authors: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors: Yasuhiro
authors: Y
authors: Shinkai
authors: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Toho University, 2-2-1 Miyama, Funabashi, 274-8510, Japan.
authors: Chika
authors: C
authors: Yamamoto
authors: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, 192-0392, Japan.
authors: Yasuyuki
authors: Y
authors: Fujiwara
authors: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors: Yoshito
authors: Y
authors: Kumagai
authors: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
authors: Toshiyuki
authors: T
authors: Kaji
mesh_terms: D000818:Animals; D058578:Biglycan / Q000235:genetics*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D020868:Gene Silencing; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053671:Syndecan-4 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D058578:Biglycan; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053671:Syndecan-4; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human
keywords: BIGLYCAN; ENDOTHELIAL CELL; PROTEOGLYCAN; SYNDECAN-4; TGF-β