Kynurenine Metabolism in the Fat Body Non-autonomously Regulates Imaginal Disc Repair in Drosophila.

Kynurenine Metabolism in the Fat Body Non-autonomously Regulates Imaginal Disc Repair in Drosophila.
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DOI:
10.1016/j.isci.2020.101738
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发表时间:
2020-12-18
期刊:
影响因子:
5.8
通讯作者:
Miura M
Miura M
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Kashio S;Miura M

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组织的相互作用是维持体内平衡的关键,然而,很少有人知道远程组织如何调节再生。在此之前,我们建立了一个遗传双系统,诱导细胞消融果蝇幼虫成虫盘,同时操纵基因在非受损组织。使用体液代谢组分析和遗传损伤系统,我们发现脂肪体中的色氨酸(Trp)-犬尿氨酸(Kyn)途径是椎间盘修复所需的。对脂肪体中Trp-Kyn代谢的遗传操纵会损害椎间盘再生,但不会影响翅膀发育。特别是,脂肪体来源的体液犬尿烯酸(KynA)是椎间盘修复所必需的。在椎间盘修复的早期阶段,脂肪体中甲硫氨酸(Met)合成S-腺苷甲硫氨酸(SAM)的损伤阻碍了血淋巴中KynA水平的维持,这表明Met-SAM和Trp-Kyn代谢之间存在联系。我们的数据表明,来自脂肪体的KynA作为组织修复和再生的容许代谢物。果蝇幼虫脂肪体中的Trp-Kyn通路是椎间盘修复的远程需要脂肪体来源的体液KynA是椎间盘修复所需的脂肪体中的SAM合成影响椎间盘修复期间血淋巴中的KynA水平生物科学;细胞生物学;发育生物学;分子生物学
Tissue interactions are critical for maintaining homeostasis; however, little is known about how remote tissue regulates regeneration. Previously, we established a genetic dual system that induces cell ablation in Drosophila larval imaginal discs and simultaneously manipulates genes in non-damaged tissues. Using humoral metabolome analysis and a genetic damage system, we found that the Tryptophan (Trp)-Kynurenine (Kyn) pathway in the fat body is required for disc repair. Genetic manipulation of Trp-Kyn metabolism in the fat body impaired disc regeneration without affecting wing development. In particular, the fat body-derived humoral kynurenic acid (KynA) was required for disc repair. The impairment of S-adenosylmethionine (SAM) synthesis from methionine (Met) in the fat body hampers the maintenance of KynA levels in hemolymph at the early stage of disc repair, suggesting a connection between Met-SAM and Trp-Kyn metabolisms. Our data indicate KynA from the fat body acts as a permissive metabolite for tissue repair and regeneration. Trp-Kyn pathway in Drosophila larval fat body is remotely required for disc repair The fat body-derived humoral KynA is required for disc repair SAM synthesis in the fat body affects KynA levels in hemolymph during disc repair Biological Sciences; Cell Biology; Developmental Biology; Molecular Biology
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