Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor <i>β</i>

Hildebrand, A.; Romaris, Manuel; Rasmussen, Lars Melholt; Heinegård, Dick; Twardzik, Daniel R.; Border, Wayne A.; Ruoslahti, Erkki

doi:10.1042/bj3020527

Cited by 938 publications

(751 citation statements)

References 52 publications

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“…Taken together, these results indicate that biglycan acts as a co‐receptor in the TGF‐β 1 –ALK5–Smad2/3 system and is involved in the downregulation of syndecan‐4 expression in vascular endothelial cells. Biglycan has been reported to bind not only TGF‐β 1 [Hildebrand et al, 1994] but also other cytokines such as tumor necrosis factor‐α [Tufvesson and Westergren‐Thorsson, 2002] and receptors [Schaefer et al, 2005]. The present study, for the first time, revealed that biglycan serves as a co‐receptor in TGF‐β signaling and this signaling downregulates the expression of syndecan‐4 in vascular endothelial cells.…”

Section: Discussionsupporting

confidence: 56%

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Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β₁ and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

Hara

Yoshida

Shinkai

et al. 2017

J of Cellular Biochemistry

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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‐β1 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‐β1 or the transforming growth factor‐β1 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‐β1 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.

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Section: Discussionsupporting

confidence: 56%

“…3), because an interaction between biglycan and TGF‐β 1 has been reported [Hildebrand et al, 1994]. TGF‐β 1 elevated the expression levels of syndecan‐4 mRNA after a 3‐h treatment at 1 and 5 ng/mL or after a 6‐h treatment at 5 ng/mL (Fig.…”

Section: Resultsmentioning

confidence: 72%

Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β₁ and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

Hara

Yoshida

Shinkai

et al. 2017

J of Cellular Biochemistry

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“…Indeed, by expressing collagens and fibronectin essential for assembling conduits, FDC may help to regulate the transport of low-molecular-weight proteins [32]. The pericellular localization of biglycan (Fig 4A) is in line with the notion that biglycan functions as an extracellular regulator of cytokines and growth factors [29][30].Beyond this, FDC may contribute to the mobility of B cells in the GC. Thus, two-photon microscopy has shown that fibroblastic reticular cells guide the migration of T cell through the T-cell zone [33] and FDC may regulate B-cell motility in a similar way [34,35].…”

supporting

confidence: 59%

“…3), known to control the availability of cytokines, chemokines and growth factors [29][30][31]. Indeed, by expressing collagens and fibronectin essential for assembling conduits, FDC may help to regulate the transport of low-molecular-weight proteins [32].…”

Section: Discussionmentioning

confidence: 99%

In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3^hi stromal cells isolated from SCID mice

et al. 2010

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Organization of the stromal compartments in secondary lymphoid tissue is a prerequisite for an efficient immune reaction. In particular, follicular dendritic cells (FDC) are pivotal for the activation and differentiation of B cells. To investigate the development of FDC, FDC together with tightly associated B cells (FDC networks) were micro-dissected from frozen tissue sections and follicular B cells were sorted by FACS. Using an in silico subtraction approach, gene expression of FDC was determined and compared with that of follicular stromal cells microdissected from the spleen of SCID mice. Nearly 90% of the FDC genes were expressed in follicular stromal cells of the SCID mouse, providing further evidence that FDC develop from the residual network of reticular cells. Thus, it suggests that rather minor modifications in the gene expression profile are sufficient for differentiation into mature FDC. The analysis of different immune-deficient mouse strains shows that a complex pattern of gene regulation controls the development of residual stromal cells into mature FDC. The in silico subtraction approach provides a molecular framework within which to determine the diverse roles of FDC in support of B cells and to investigate the differentiation of FDC from their mesenchymal precursor cells. [1][2][3][4]. The network of FDC is a micro-environment required for the survival of follicular B cells and is also a prerequisite for an efficient GC reaction. At the early stage of GC development FDC support B-cell proliferation, whereas at the later stages FDC have an important function in the selection and differentiation of high affinity B cells to memory and plasma cells [1,5].Although FDC are crucial for B-cell development, our knowledge of FDC transcriptional activity remains marginal. FDC are fragile cells and are tightly associated with B cells -properties that have thus far hampered the isolation of pure FDC populations [6][7]. To overcome these problems, FDC lines have been established, however, as these cells are maintained over several weeks in culture, their phenotype no longer reflects the in vivo situation [8][9][10][11][12][13]. A number of different approaches for the enrichment and gene expression analysis of FDC have been shown to be more representative of the in vivo situation [6,8,11].From a number of experiments, it is apparent that FDC are a highly specialized subset of reticular cells [14][15][16][17][18]. Using BP3, an ectoenzyme of the NAD glycohydrolase family, as a marker antigen for the splenic reticular network of stromal cells, one can distinguish the reticulum cells in the B-cell area from those in the T-cell zone. High expression of BP3 defines the follicle, the area to which B cells To identify molecular markers defining a developmental relationship between mature FDC and the BP3 hi reticular cells of SCID mice, gene expression profiles were determined. Using an in silico subtraction approach, we were able to identify a novel set of genes that showed specific expression in FDC. When gene ex...

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“…Bgn and Dcn belong to the class I type SLRP and are highly expressed in skeletal and connective tissues (1,12,14,15,31). The exact function of both Bgn and Dcn are unknown, however both can bind and modulate members of the TGF-beta superfamily (11).…”

Section: Introductionmentioning

confidence: 99%

Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice

Wadhwa

Ortiz

et al. 2007

Bone

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Biglycan (Bgn) and decorin (Dcn) are highly expressed in numerous tissues in the craniofacial complex. However, their expression and function in the cranial sutures is unknown. In order to study this, we first examined the expression of biglycan and decorin in the posterior frontal suture (PFS), which predictably fuses between 21-45 days post-natal and in the non-fusing sagittal (S) suture from wildtype (Wt) mice. Our data showed that Bgn and Dcn were expressed in both cranial sutures. We then characterized the cranial suture phenotype in Bgn deficient, Dcn deficient, Bgn/Dcn double deficient, and Wt mice. At embryonic day 18.5, alizarin red/ alcian blue staining showed that the Bgn/Dcn double deficient mice had hypomineralization of the frontal and parietal craniofacial bones. Histological analysis of adult mice (45-60 days post natal) showed that the Bgn or Dcn deficient mice had no cranial suture abnormalities and immunohistochemistry staining showed increased production of Dcn in the PFS from Bgn deficient mice. To test possible compensation of Dcn in the Bgn deficient sutures we examined the Bgn/Dcn double deficient mice and found they had impaired fusion of the PFS. Semi-quantitative RT-PCR analysis of RNA from 35 day-old mice revealed increased expression of Bmp-4 and Dlx-5 in the PFS compared to their non-fusing S suture in Wt tissues and decreased expression of Dlx-5 in both PF and S sutures in the Bgn/Dcn double deficient mice compared to the Wt mice. Failure of PFS fusion and hypomineralization of the calvaria in the Bgn/Dcn double deficient mice demonstrate these extracellular matrix proteoglycans could have a role in controlling the formation and growth of the cranial vault.

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Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor β

Cited by 938 publications

References 52 publications

Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β₁ and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β₁ and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3^hi stromal cells isolated from SCID mice

Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice

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Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor β

Cited by 938 publications

References 52 publications

Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β1 and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β1 and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3hi stromal cells isolated from SCID mice

Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice

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Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β₁ and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

Biglycan Intensifies ALK5–Smad2/3 Signaling by TGF‐β₁ and Downregulates Syndecan‐4 in Cultured Vascular Endothelial Cells

In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3^hi stromal cells isolated from SCID mice