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Blood:清华大学揭示TGF-β与MVP-1的关系

来源:生物谷 2007-02-05 08:45

    清华大学生物科学与技术系生物膜与膜生物工程国家重点实验室、中国科学院遗传与发育研究所的研究人员在2月1日Blood杂志发表文章,对单核细胞趋化蛋白-1(monocyte  chemoattractant  protein-1,MCP-1)介导的转化生长因子β(Transforming  growth  factor-β,TGF-β)诱导血管生成(angiogenesis)机制做了进一步揭示。

    TGF-β及其信号途径调节物在血管形成过程中扮演重要角色。Jing  Ma(马江,音译)等先前研究发现,MCP-1是内皮细胞(endothelial  cells  ,ECs)TGF-β靶标基因之一。

    最近,马江等发现MCP-1通过向ECs募集血管平滑肌细胞(vascular  smooth  muscle  cells  ,VSMCs)和间充质细胞(mesenchymal  cells),介导TGF-β的血管生成作用。研究人员通过鸡胚脲囊膜技术(chick  chorioallantoic  membrane  assay)发现,TGF-β促进形成新的血管,用MCP-1中和抗体抑制MCP-1的活性,TGF-β这种促进血管形成的作用被削弱。

    Wound  healing  和transwell检验结果证明MCP-1有诱导物的功能,刺激WSMCs和间叶细胞10T1/2向ECs迁移。更进一步研究发现,TGF-β处理过的ESs细胞会刺激VSMC迁移,抑制MCP-1活性将削弱TGF-β诱导的VSMC向ECs的迁移。最后,研究人员发现MCP-1是TGF-β经由Smad3/4的靶标基因。

    总结来看,实验结果提示MCP-1通过增强壁细胞(mural  cells)向ECs迁移,介导TGF-β刺激的血管生成,进而促进新生血管成熟。

    transwell侵袭实验原理:简单地说就是用一层膜将高营养的培养液和低营养的培养液隔开,放在低营养培养液里的细胞会向高营养培养液里移动,但需要穿过膜。研究人员在膜上涂上一层类似于细胞外基质的基质胶,细胞要把基质消化才可以从低营养的培养液跑到高营养的培养液里面,于是可以通过检测高营养培养液里细胞量获知细胞的侵袭能力。

原始出处:

Blood, 1 February 2007, Vol. 109, No. 3, pp. 987-994.

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

MCP-1 mediates TGF-ß–induced angiogenesis by stimulating vascular smooth muscle cell migration

Jing Ma1, Qiang Wang1, Teng Fei1, Jing-Dong Jackie Han2, and Ye-Guang Chen1

From the1 State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China; and 2 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

Transforming growth factor-ß (TGF-ß) and its signaling mediators play crucial roles in vascular formation. Our previous microarray analysis identified monocyte chemoattractant protein-1 (MCP-1) as a TGF-ß target gene in endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic effect of TGF-ß by recruiting vascular smooth muscle cells (VSMCs) and mesenchymal cells toward ECs. By using a chick chorioallantoic membrane assay, we show that TGF-ß promotes the formation of new blood vessels and this promotion is attenuated when MCP-1 activity is blocked by its neutralizing antibody. Wound healing and transwell assays established that MCP-1 functions as a chemoattractant to stimulate migration of VSMCs and mesenchymal 10T1/2 cells toward ECs. Furthermore, the conditioned media from TGF-ß–treated ECs stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF-ß–induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene target of TGF-ß via Smad3/4. Taken together, our findings suggest that MCP-1 mediates TGF-ß–stimulated angiogenesis by enhancing migration of mural cells toward ECs and thus promoting the maturation of new blood vessels.


相关报道:

TGF-β样品的处理和保存

SMAD3介导TGF-β1刺激软骨细胞增殖和抑制软骨细胞肥大性分化

Smads蛋白家族与TGF-β的细胞内信号转导

尿转移生长因子-β1(TGF-β1)

TGF对牙齿发育的调节

转化生长因子与脑缺血

单核细胞趋化蛋白-1(MCP-1)

趋化因子系列(MCP-1)(MSP)酶联免疫法

华中科大克隆成功新的血管生成因子

血管生成的研究进展

日发现新的血管生成抑制剂可阻断小鼠胃癌

通心络促血管生成作用的实验研究

血管生成素相互作用蛋白的发现及其在哺乳动物细胞中的验证

 

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