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Circulation Research:离子通道TRPC1在血管发育过程中的重要作用

来源:上海生命科学研究院 2010-03-09 09:22

2月25日,《循环研究》(Circulation Research)在线发表了中国科学院上海生命科学研究院神经科学研究所杜久林研究组的研究论文TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish。该论文揭示了离子通道TRPC1对于血管生成(angiogenesis)的重要作用。这项工作是由于蓬春、顾珊烨和卜纪雯合作完成。

人体在发育过程和许多疾病状态下都伴随着大量的血管生成,因此了解血管生成的分子机理具有非常重要的生理和病理意义。科研人员利用斑马鱼作为血管生成的活体研究模型,发现下调离子通道TRPC1可以显著的影响顶端血管内皮细胞的迁移、增殖和丝状伪足的伸展,从而导致血管生成的缺陷。他们进一步的研究还发现,TRPC1对于过表达血管内皮生长因子(VEGF)所导致的异常血管生成和胞外信号调节激酶(ERK)磷酸化的升高是必需的,表明TRPC1是通过介导VEGF的作用来影响血管生长的。这一研究首次利用活体模型揭示了TRPC1对于血管生成的重要作用,同时也暗示TRPC1可能可以用作治疗病理性血管生成的药物靶点。

该研究得到了中国科学院、科技部和上海市科委的基金资助。(生物谷Bioon.com)

生物谷推荐原始出处:

Circulation Research. 2010 doi: 10.1161/CIRCRESAHA.109.207670

TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish

Peng-chun Yu ; Shan-ye Gu ; Ji-wen Bu ; and Jiu-lin Du *

From the Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.

Rationale: Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development.

Objective: To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development.

Methods and Results: Knockdown of zebrafish trpc1 by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide–resistant form of zebrafish trpc1 mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell–autonomous. In vivo, time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. Furthermore, Trpc1 acted synergistically with vascular endothelial growth factor A (Vegf-a) in controlling ISV growth, and appeared to be downstream to Vegf-a in controlling angiogenesis, as evidence by the findings that Trpc1 was required for Vegf-a–induced ectopic angiogenesis of subintestinal veins and phosphorylation of extracellular signal-regulated kinase.

Conclusions: These results provide the first in vivo evidence that TRPC1 is essential for angiogenesis, reminiscent of the role of TRPCs in axon guidance. It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis.

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