Dataset Information

Transforming Growth Factor-?1 Modulates 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-?1 (TGF-?1 ) 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-?1 first upregulates and then downregulates the expression of syndecan-4, a transmembrane heparan sulfate proteoglycan, via the TGF-? 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-?1 . 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-?1 , 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-?1 . J. Cell. Biochem. 118: 2009-2017,2017. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

SUBMITTER: Hara T

PROVIDER: S-EPMC5485002 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Transforming Growth Factor-β1 Modulates the Expression of Syndecan-4 in Cultured Vascular Endothelial Cells in a Biphasic Manner.

Hara Takato T Yoshida Eiko E Fujiwara Yasuyuki Y Yamamoto Chika C Kaji Toshiyuki T

Journal of cellular biochemistry 20170410 8

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-β1 first upregulates and then downregulates the expression of ...[more]

PMID: 28019669

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Project description:Appropriate growth and development of the endometrium across the menstrual cycle is key for a woman's quality of life and reproductive well-being. Recurrent pregnancy loss (RPL) and heavy menstrual bleeding (HMB) affect a significant proportion of the female population worldwide. These endometrial pathologies have a significant impact on a woman's quality of life as well as placing a high economic burden on a country's health service. An underlying cause for both conditions is unknown in approximately 50% of cases. Previous research has demonstrated that aberrant endometrial vascular maturation is associated with both RPL and HMB, where it is increased in RPL but reduced in HMB. TGFβ1 is one of the key growth factors that regulate vascular maturation, by inducing phenotypic switching of vascular smooth muscle cells (VSMCs) from a synthetic phenotype to a more contractile one. Our previous data demonstrated an increase in TGFβ1 in the endometrium of RPL, while others have shown a decrease in women with HMB. However, TGFβ1 bioavailability is tightly controlled, and we therefore sought to perform an extensive immunohistochemical analysis of different components in the pathway in the endometrium of normal controls, women with HMB or RPL. In addition, two in vitro models were used to examine the role of TGFβ1 in endometrial vascular maturation and endothelial cell (EC):VSMC association. Taken all together, the immunohistochemical data suggest a decrease in bioavailability, receptor binding capacity, and signaling in the endometrium of women with HMB compared with controls. In contrast, there is an increase in the bioavailability of active TGFβ1 in the endometrium of women with RPL compared with controls. Endometrial explants cultured in TGFβ1 had an increase in the number of vessels associated with contractile VSMC markers, although the total number of vessels did not increase. In addition, TGFβ1 increased EC:VSMC association in an in vitro model. In conclusion, TGFβ1 is a key regulator of endometrial vascular maturation and could be considered as a therapeutic target for women suffering from HMB and/or RPL.

Dataset Information

Transforming Growth Factor-?1 Modulates the Expression of Syndecan-4 in Cultured Vascular Endothelial Cells in a Biphasic Manner.

Publications

Transforming Growth Factor-β<sub>1</sub> Modulates the Expression of Syndecan-4 in Cultured Vascular Endothelial Cells in a Biphasic Manner.

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