2月25日,，《循環(huán)研究》（Circulation Research）在線發(fā)表了中國(guó)科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所杜久林研究組的研究論文TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish。該論文揭示了離子通道TRPC1對(duì)于血管生成（angiogenesis）的重要作用,。這項(xiàng)工作是由于蓬春、顧珊燁和卜紀(jì)雯合作完成,。
人體在發(fā)育過(guò)程和許多疾病狀態(tài)下都伴隨著大量的血管生成,，因此了解血管生成的分子機(jī)理具有非常重要的生理和病理意義?？蒲腥藛T利用斑馬魚(yú)作為血管生成的活體研究模型,，發(fā)現(xiàn)下調(diào)離子通道TRPC1可以顯著的影響頂端血管內(nèi)皮細(xì)胞的遷移、增殖和絲狀偽足的伸展,，從而導(dǎo)致血管生成的缺陷,。他們進(jìn)一步的研究還發(fā)現(xiàn)，TRPC1對(duì)于過(guò)表達(dá)血管內(nèi)皮生長(zhǎng)因子（VEGF）所導(dǎo)致的異常血管生成和胞外信號(hào)調(diào)節(jié)激酶（ERK）磷酸化的升高是必需的,，表明TRPC1是通過(guò)介導(dǎo)VEGF的作用來(lái)影響血管生長(zhǎng)的,。這一研究首次利用活體模型揭示了TRPC1對(duì)于血管生成的重要作用，同時(shí)也暗示TRPC1可能可以用作治療病理性血管生成的藥物靶點(diǎn),。
該研究得到了中國(guó)科學(xué)院,、科技部和上海市科委的基金資助。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
