Dataset Information

Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-?₁ and 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-?₁ signaling 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-?₁ or the transforming growth factor-?₁ type 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-?₁ signaling pathway that mediates the suppression of syndecan-4 expression in vascular endothelial cells. J. Cell. Biochem. 118: 1087-1096, 2017. © 2016 Wiley Periodicals, Inc.

SUBMITTER: Hara T

PROVIDER: S-EPMC6221004 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-β<sub>1</sub> and Downregulates Syndecan-4 in Cultured Vascular Endothelial Cells.

Hara Takato T Yoshida Eiko E Shinkai Yasuhiro Y Yamamoto Chika C Fujiwara Yasuyuki Y Kumagai Yoshito Y Kaji Toshiyuki T

Journal of cellular biochemistry 20170110 5

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 pro ...[more]

PMID: 27585241

Similar Datasets

Project description:AimsVascular calcification is a major cause of morbidity and mortality. Fibroblast growth factor-2 (FGF-2) plays an instructive role in osteogenesis and bone development, but its role in vascular calcification was unknown. Therefore, we investigated the involvement of FGF-2 in vascular calcification and determined the mechanism by which it regulates this process.Methods and resultsWe demonstrate that FGF-2 expression is increased in vascular smooth muscle cells (VSMCs) induced to deposit a mineralized matrix by incubation with ?-glycerophosphate. FGF-2 is also localized to sites of calcification within human atherosclerotic plaques. The expression of syndecan-4, a heparan sulfate proteoglycan which regulates FGF-2 signalling, is also increased in mineralizing VSMCs and co-localizes with FGF-2 in human calcified atherosclerotic plaques. Exogenous FGF-2 inhibits VSMC mineralization, and this inhibition is reduced when syndecan-4 expression is knocked-down using siRNA. Biochemical inhibition of FGFR signalling using a pan FGFR inhibitor (BGJ398) or knocking-down syndecan-4 expression in VSMCs using siRNA increases VSMC mineralization. These increases are prevented by inhibiting transforming growth factor-? (TGF?) signalling with SB431542, suggesting cross-talk between FGF-2 and TGF? signalling is crucial for the regulation of VSMC mineralization. Syndecan-4 can also regulate FGF-2 signalling directly via protein kinase C? (PKC?) activation. Biochemical inhibition of PKC? activity using Gö6976, or siRNA-mediated suppression of PKC? expression increases VSMC mineralization; this increase is also prevented with SB431542. Finally, the ability of FGF-2 to inhibit VSMC mineralization is reduced when PKC? expression is knocked-down.ConclusionThis is the first demonstration that syndecan-4 promotes FGF-2 signalling, and in turn, suppresses VSMC mineralization by down-regulating TGF? signalling. Our discoveries that FGF-2 and syndecan-4 expression is increased in mineralizing VSMCs and that PKC? regulates FGF-2 and TGF? signalling in VSMCs suggests that the syndecan-4/FGF-2/TGF? signalling axis could represent a new therapeutic target for vascular calcification.

Dataset Information

Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-?1 and Downregulates Syndecan-4 in Cultured Vascular Endothelial Cells.

Publications

Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-β<sub>1</sub> and Downregulates Syndecan-4 in Cultured Vascular Endothelial Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-?₁ and Downregulates Syndecan-4 in Cultured Vascular Endothelial Cells.