Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China.
Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
Mech Ageing Dev. 2022 Jun;204:111673. doi: 10.1016/j.mad.2022.111673. Epub 2022 Apr 6.
Gut homeostasis is a dynamically balanced state to maintain intestinal health. Vacuolar ATPases (V-ATPases) are multi-subunit proton pumps that were driven by ATP hydrolysis. Several subunits of V-ATPases may be involved in the maintenance of intestinal pH and gut homeostasis in Drosophila. However, the specific role of each subunit in this process remains to be elucidated. Here, we knocked down the Drosophila gene VhaAC39-1 encoding the V0d1 subunit of V-ATPases to assess its function in gut homeostasis. Knockdown of VhaAC39-1 resulted in the loss of midgut acidity, the increase of the number of gut microbiota and the impairment of intestinal epithelial integrity in flies. The knockdown of VhaAC39-1 led to the hyperproliferation of intestinal stem cells, increasing the number of enteroendocrine cells, and activated IMD signaling pathway and JAK-STAT signaling pathway, inducing intestinal immune response of Drosophila. In addition, knockdown of VhaAC39-1 caused the disturbance of many physiological indicators such as food intake, triglyceride level and fecundity of flies, which ultimately led to the shortening of the life span of Drosophila. These results shed light on the gut homeostasis mechanisms which would help to identify interventions to promote healthy aging.
肠道内环境稳态是维持肠道健康的一种动态平衡状态。液泡型三磷酸腺苷酶（V-ATPases）是由 ATP 水解驱动的多亚基质子泵。V-ATPases 的几个亚基可能参与了果蝇肠道 pH 值和肠道内环境稳态的维持。然而，每个亚基在这个过程中的具体作用仍有待阐明。在这里，我们敲低了果蝇基因 VhaAC39-1，该基因编码 V-ATPases 的 V0d1 亚基，以评估其在肠道内环境稳态中的功能。VhaAC39-1 的敲低导致中肠酸度丧失、肠道微生物数量增加以及肠道上皮完整性受损。VhaAC39-1 的敲低导致肠道干细胞过度增殖，肠内分泌细胞数量增加，并激活 IMD 信号通路和 JAK-STAT 信号通路，诱导果蝇肠道免疫反应。此外，VhaAC39-1 的敲低导致果蝇的许多生理指标紊乱，如摄食量、甘油三酯水平和繁殖力，最终导致果蝇寿命缩短。这些结果揭示了肠道内环境稳态的机制，这有助于确定促进健康衰老的干预措施。
