昆蟲體內(nèi)的循環(huán)系統(tǒng)一般不參與氧氣運輸,，各組織和器官所需的氧氣直接由氣管系統(tǒng)供應(yīng),。與哺乳動物的血管生成過程相似,，昆蟲氣管的末端也能夠產(chǎn)生分枝并侵入缺氧組織內(nèi),。
以往研究表明,，果蠅體內(nèi)處于缺氧狀態(tài)的細(xì)胞會產(chǎn)生Bnl,，這是成纖維細(xì)胞生長因子的同源體,，其受體Btl位于氣管細(xì)胞表面，Bnl能夠誘導(dǎo)氣管細(xì)胞分枝伸入缺氧組織內(nèi),，這就是氣管生成的“Bnl中心模式”,。
Centanin等人的研究工作進一步揭示了氣管末端分枝的形成機制，果蠅氣管末端的細(xì)胞本身對缺氧環(huán)境也非常敏感,，缺氧條件下,，對氧含量敏感的脯氨酰羥化酶Fatiga能夠增加缺氧誘導(dǎo)因子Similar（Sima）的濃度，Sima是人類缺氧誘導(dǎo)因子（HIFs）的同源分子,，能夠誘導(dǎo)Btl的表達,，增加氣管末端細(xì)胞中Btl的濃度，促使細(xì)胞產(chǎn)生分枝,。而在非氣管細(xì)胞內(nèi),，Sima能夠誘導(dǎo)Bnl的表達，但也可能有其它一些因子參與該過程,。
研究人員指出,，氣管末端細(xì)胞在缺氧條件下通過自主反應(yīng)，增加其表面受體Btl的濃度,，能夠使其對組織Bnl水平增加更加敏感,，是缺氧誘導(dǎo)氣管分枝的重要步驟。此即“搜索模式”,，和此前的“Bnl中心模式”一起更好解釋了氣管分枝發(fā)生的機制,，這一理論對哺乳動物的血管發(fā)生機制也有一定的啟示。
該研究以封面論文形式發(fā)表于4月15日的《發(fā)育細(xì)胞》（Developmental Cell）上,。（科學(xué)網(wǎng) 穆宏平/編譯）
生物谷推薦原始出處：
（Developmental Cell）,，Vol 14, 547-558, 15 April 2008,，Lázaro Centanin, Pablo Wappner
Cell Autonomy of HIF Effects in Drosophila: Tracheal Cells Sense Hypoxia and Induce Terminal Branch Sprouting
Lázaro Centanin,1,4 Andrés Dekanty,1 Nuria Romero,1 Maximiliano Irisarri,1 Thomas A. Gorr,2,3 and Pablo Wappner1,3,
1 Instituto Leloir and FBMC, FCEyN-Universidad de Buenos Aires, CONICET, Patricias Argentinas 435, Buenos Aires 1405, Argentina
2 Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Wintherthurerstrasse 260, CH-8057 Zurich, Switzerland
Summary
Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections toward oxygen-starved areas, in a process analogous to mammalian angiogenesis. This response involves the upregulation of FGF/Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells. Here, we show that extra sprouting depends on the Hypoxia-Inducible Factor (HIF)-α homolog Sima and on the HIF-prolyl hydroxylase Fatiga that operates as an oxygen sensor. In mild hypoxia, Sima accumulates in tracheal cells, where it induces breathless, and this induction is sufficient to provoke tracheal extra sprouting. In nontracheal cells, Sima contributes to branchless induction, whereas overexpression of Sima fails to attract terminal branch outgrowth, suggesting that HIF-independent components are also required for full induction of the ligand. We propose that the autonomous response to hypoxia that occurs in tracheal cells enhances tracheal sensitivity to increasing Branchless levels, and that this mechanism is a cardinal step in hypoxia-dependent tracheal sprouting.
