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Syndecan-1通过抑制培养的血管内皮细胞中的ERK1/2和p38 MAPK信号通路来下调Syndecan-4的表达。

Syndecan-1 downregulates syndecan-4 expression by suppressing the ERK1/2 and p38 MAPK signaling pathways in cultured vascular endothelial cells.

作者信息

Hara Takato, Sato Arisa, Yamamoto Chika, Kaji Toshiyuki

机构信息

Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.

Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.

出版信息

Biochem Biophys Rep. 2021 Apr 24;26:101001. doi: 10.1016/j.bbrep.2021.101001. eCollection 2021 Jul.

Abstract

Syndecan-1 and syndecan-4 are members of the syndecan family of transmembrane heparan sulfate proteoglycans. Vascular endothelial cells synthesize both species of proteoglycans and use them to regulate the blood coagulation-fibrinolytic system and their proliferation their heparin-like activity and FGF-2 binding activity, respectively. However, little is known about the crosstalk between the expressions of the proteoglycan species. Previously, we reported that biglycan, a small leucine-rich dermatan sulfate proteoglycan, intensifies ALK5-Smad2/3 signaling by TGF-β and downregulates syndecan-4 expression in vascular endothelial cells. In the present study, we investigated the crosstalk between the expressions of syndecan-1 and other proteoglycan species (syndecan-4, perlecan, glypican-1, and biglycan) in bovine aortic endothelial cells in a culture system. These data suggested that syndecan-1 downregulated syndecan-4 expression by suppressing the endogenous FGF-2-dependent ERK1/2 pathway and FGF-2-independent p38 MAPK pathway in the cells. Moreover, this crosstalk was a one-way communication from syndecan-1 to syndecan-4, suggesting that syndecan-4 compensated for the reduced activity in the regulation of vascular endothelial cell functions caused by the decreased expression of syndecan-1 under certain conditions.

摘要

Syndecan-1和syndecan-4是跨膜硫酸乙酰肝素蛋白聚糖syndecan家族的成员。血管内皮细胞合成这两种蛋白聚糖,并分别利用它们调节血液凝固-纤维蛋白溶解系统及其增殖、肝素样活性和FGF-2结合活性。然而,关于这两种蛋白聚糖表达之间的相互作用知之甚少。此前,我们报道富含亮氨酸的小分子硫酸皮肤素蛋白聚糖双糖链蛋白聚糖可增强TGF-β介导的ALK5-Smad2/3信号传导,并下调血管内皮细胞中syndecan-4的表达。在本研究中,我们在培养系统中研究了牛主动脉内皮细胞中syndecan-1与其他蛋白聚糖(syndecan-4、基底膜聚糖、磷脂酰肌醇蛋白聚糖-1和双糖链蛋白聚糖)表达之间的相互作用。这些数据表明,syndecan-1通过抑制细胞内内源性FGF-2依赖的ERK1/2途径和FGF-2非依赖的p38 MAPK途径下调syndecan-4的表达。此外,这种相互作用是从syndecan-1到syndecan-4的单向通讯,表明在某些条件下,syndecan-4可补偿因syndecan-1表达降低而导致的血管内皮细胞功能调节活性降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7263/8099740/25a089b0075c/ga1.jpg

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