Kashio Soshiro, Miura Masayuki
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
iScience. 2020 Nov 6;23(12):101738. doi: 10.1016/j.isci.2020.101738. eCollection 2020 Dec 18.
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 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.
组织间相互作用对于维持体内平衡至关重要；然而，关于远端组织如何调节再生却知之甚少。此前，我们建立了一种基因双系统，可在幼虫成虫盘诱导细胞消融，并同时操纵未受损组织中的基因。利用体液代谢组分析和基因损伤系统，我们发现脂肪体中的色氨酸（Trp）-犬尿氨酸（Kyn）途径是盘修复所必需的。脂肪体中Trp-Kyn代谢的基因操纵会损害盘再生，而不影响翅发育。特别是，脂肪体衍生的体液犬尿酸（KynA）是盘修复所必需的。脂肪体中蛋氨酸（Met）合成S-腺苷甲硫氨酸（SAM）的受损会阻碍盘修复早期血淋巴中KynA水平的维持，这表明Met-SAM与Trp-Kyn代谢之间存在联系。我们的数据表明，来自脂肪体的KynA作为一种许可性代谢物，对组织修复和再生起作用。
