Regulation of glycosmainoglycan chain formation in proteoglycan molecules synthesized by brain vascular cells

脑血管细胞合成的蛋白聚糖分子中糖主聚糖链形成的调节

• 批准号: 16590070
• 负责人: KAJI Toshiyuki
• 金额: $ 2.3万
• 依托单位: Hokuriku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590070/
• 关键词: Vascular; Endothelial cell; Pericyte; Proteoglycan; Glycosaminoglycan; Heparan sulfate; Chondroitin sulfate; Dermatan sulfate

A member of the vascular endothelial growth factor (VEGF) family, VEGF165 regulates vascular endothelial cell functions in autocrine and paracrine fashions in microvessels. Proteoglycans are highly glycosylated poly-anionic macromolecules that influence cellular behaviors such as proliferation and migration by interacting with cytokines/growth factors. In the present study, we investigated the regulation of proteoglycan synthesis by VEGF165 in cultured human brain microvascular endothelial cells. The cells were exposed to recombinant human VEGF165, and the proteoglycans were then characterized using biochemical techniques. VEGF165 treatment increased the accumulation of proteoglycans 1.4- and 1.6-fold in the cell layer and conditioned medium, respectively. This effect resulted from the activation of VEGFR2, and was mimicked by vammin, a VEGFR2 ligand from snake venom but not placenta growth factor, which binds specifically to VEGFRI. VEGF165 stimulated the production and secretion of perlecan, substituted with shorter heparan sulfate side chains, but with unaltered sulfated disaccharide composition. The perlecan secreted by VEGF 165 -stimulated endothelial cells may be involved in the regulation of cellular behavior during angiogenesis, in diseases of the brain microvessels, and in the maintenance of the endothelial cell monolayer.

VEGF165 是血管内皮生长因子 (VEGF) 家族的成员，以自分泌和旁分泌的方式调节微血管中的血管内皮细胞功能。蛋白聚糖是高度糖基化的聚阴离子大分子，通过与细胞因子/生长因子相互作用影响细胞行为，例如增殖和迁移。在本研究中，我们研究了 VEGF165 在培养的人脑微血管内皮细胞中对蛋白聚糖合成的调节。将细胞暴露于重组人 VEGF165，然后使用生化技术对蛋白聚糖进行表征。 VEGF165处理使细胞层和条件培养基中蛋白聚糖的积累分别增加1.4倍和1.6倍。这种效应是由 VEGFR2 的激活引起的，并且被 vammin 模仿，vammin 是一种来自蛇毒的 VEGFR2 配体，但不是胎盘生长因子，它与 VEGFRI 特异性结合。 VEGF165 刺激基底膜聚糖的产生和分泌，并用较短的硫酸乙酰肝素侧链取代，但硫酸化二糖组成未改变。 VEGF 165 刺激的内皮细胞分泌的基底膜聚糖可能参与血管生成过程中细胞行为的调节、脑微血管疾病以及内皮细胞单层的维持。

项目成果

Identification and functions of chondroitin sulfate in the milieu of neural stem cells

• DOI: 10.1074/jbc.m507130200
• 发表时间: 2006-03-03
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Ida, M;Shuo, T;Oohira, A
• 通讯作者: Oohira, A

Differential regulation of biglycan and decorin synthsis by connective tissue growth factor in cultured vascular endothelial cells

培养血管内皮细胞中结缔组织生长因子对双糖链蛋白聚糖和核心蛋白聚糖合成的差异调节

• 发表时间: 2004
• 期刊: Biochemical and Biophysical Research Communications 322
• 作者: Oka;S.et al.;Kaji T et al.
• 通讯作者: Kaji T et al.

Induction of synthesis of a large heparan sulfate proteoglycan, perlecan, by thrombin in cultured human coronary smooth muscle cells.

在培养的人冠状平滑肌细胞中通过凝血酶诱导合成大的硫酸乙酰肝素蛋白聚糖（基底膜聚糖）。

• 发表时间: 2005
• 期刊: Biochimica et Biophysica Acta 1722
• 作者: 今井輝子;井本真澄;坂本久恵;橋本 満;Michiru Ida;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto
• 通讯作者: Chika Yamamoto

Proteoglycan synthesis is not influenced by zinc in proliferating bovine aortic endothelial cells in culture

• DOI: 10.1248/jhs.51.720
• 发表时间: 2005-12-01
• 期刊: JOURNAL OF HEALTH SCIENCE
• 作者: Fujiwara, Y;Plaas, AH;Kaji, T
• 通讯作者: Kaji, T

Stimulation of proteoglycan release from cultured vascular endothelial cell layers by sodium spirulan.

螺旋藻钠刺激培养的血管内皮细胞层释放蛋白多糖。

• 发表时间: 2004
• 期刊: Journal of Health Science 50・6
• 作者: 今井輝子;井本真澄;坂本久恵;橋本 満;Michiru Ida;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Yasuyuki Fujiwara;Toshiyuki Kaji
• 通讯作者: Toshiyuki Kaji