Department of Biological Sciences, University of Cyprus, Aglantzia, Cyprus.
Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA.
Nat Cell Biol. 2021 May;23(5):497-510. doi: 10.1038/s41556-021-00674-1. Epub 2021 May 10.
The Drosophila trachea, as the functional equivalent of mammalian blood vessels, senses hypoxia and oxygenates the body. Here, we show that the adult intestinal tracheae are dynamic and respond to enteric infection, oxidative agents and tumours with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated regeneration and is sufficient to drive ISC proliferation in undamaged intestines. Gut damage or tumours induce HIF-1α (Sima in Drosophila), which stimulates tracheole branching via the FGF (Branchless (Bnl))-FGFR (Breathless (Btl)) signalling cascade. Bnl-Btl signalling is required in the intestinal epithelium and the trachea for efficient damage-induced tracheal remodelling and ISC proliferation. Chemical or Pseudomonas-generated reactive oxygen species directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygenation are essential for intestinal tumour growth. We have identified a mechanism of tracheal-intestinal tissue communication, whereby damage and tumours induce neo-tracheogenesis in Drosophila, a process reminiscent of cancer-induced neoangiogenesis in mammals.
果蝇的气管作为哺乳动物血管的功能等效物，可以感知缺氧并为身体供氧。在这里，我们表明成年肠道气管是动态的，并对肠道感染、氧化应激和肿瘤做出反应，表现为终末分支增加。增加的气管化对于有效的损伤诱导肠道干细胞（ISC）介导的再生是必要的，并且足以在未受损的肠道中驱动 ISC 增殖。肠道损伤或肿瘤诱导 HIF-1α（果蝇中的 Sima），通过 FGF（无分支（Bnl））-FGFR（呼吸急促（Btl））信号级联刺激气管分支。Bnl-Btl 信号在肠道上皮细胞和气管中对于有效的损伤诱导的气管重塑和 ISC 增殖是必需的。化学物质或铜绿假单胞菌产生的活性氧直接影响气管，对于分支和肠道再生是必要的。同样，气管分支和由此增加的氧合对于肠道肿瘤生长是必不可少的。我们已经确定了气管-肠道组织通讯的机制，即损伤和肿瘤在果蝇中诱导新气管发生，这一过程让人联想到哺乳动物中癌症诱导的新血管生成。
