title: Transforming Growth Factor-β1Modulates the Expression of Syndecan-4 in Cultured Vascular Endothelial Cells in a Biphasic Manner.
abstract: Proteoglycans are macromolecules that consist of a core protein and one or more glycosaminoglycan side chains. Previously, we reported that transforming growth factor-β1(TGF-β1) regulates the synthesis of a large heparan sulfate proteoglycan, perlecan, and a small leucine-rich dermatan sulfate proteoglycan, biglycan, in vascular endothelial cells depending on cell density. Recently, we found that TGF-β1first upregulates and then downregulates the expression of syndecan-4, a transmembrane heparan sulfate proteoglycan, via the TGF-β receptor ALK5 in the cells. In order to identify the intracellular signal transduction pathway that mediates this modulation, bovine aortic endothelial cells were cultured and treated with TGF-β1. Involvement of the downstream signaling pathways of ALK5-the Smad and MAPK pathways-in syndecan-4 expression was examined using specific siRNAs and inhibitors. The data indicate that the Smad3-p38 MAPK pathway mediates the early upregulation of syndecan-4 by TGF-β1, whereas the late downregulation is mediated by the Smad2/3 pathway. Multiple modulations of proteoglycan synthesis may be involved in the regulation of vascular endothelial cell functions by TGF-β1. J. Cell. Biochem. 118: 2009-2017,2017. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Tokyo University of Science, Noda 278-8510, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Hara
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Tokyo University of Science, Noda 278-8510, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Yoshida
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Toho University, Funabashi 274-8510, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Environmental Health, Tokyo University of Science, Noda 278-8510, Japan.
authors.forename: Toshiyuki
authors.identifier: 0000-0002-7393-2656
authors.initials: T
authors.lastname: Kaji
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D053671:Syndecan-4 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D051900:Smad3 Protein; D053671:Syndecan-4; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I
keywords: ENDOTHELIAL CELL; PROTEOGLYCAN; SYNDECAN-4; TGF-β