Puri Sonali, Nath Dharmendra Kumar, Lee Youngseok
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, 02707, Republic of Korea.
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, 02707, Republic of Korea.
Insect Biochem Mol Biol. 2025 Apr;179:104267. doi: 10.1016/j.ibmb.2025.104267. Epub 2025 Feb 3.
Normal gastrointestinal (GI) motility, including defecation, is crucial for nutrient absorption, energy balance, and overall health in species ranging from insects to humans. Disruptions in GI motility can lead to conditions like constipation or severe diseases. Mechanosensors, including TRP channels and Piezo, are known to play key roles in regulating gut physiology in Drosophila melanogaster, but their precise involvement in defecation is not fully understood. Additionally, neuropeptides like DH44 have been implicated in gut regulation. This study explores the roles of Trpγ, Diuretic hormone 44 Receptor 2 (DH44R2), and Piezo in controlling feeding amount, gut motility, and defecation using genetic mutants and RNAi techniques. Mutants for these genes exhibited increased excreta production and size, whereas Dh44 and Dh44R1 mutants had a reduced number of excreta, but with increased size. Co-expression and rescue experiments further confirmed the critical roles of these genes in the same gut cells. The findings reveal that local gut-specific mechanisms are the primary drivers of defecation. The results highlight the collaboration between Trpγ, Piezo, and DH44R2 in regulating gut motility and defecation. By uncovering how these mechanosensory proteins and cells work together, this research may offer insights into human GI disorders like Irritable Bowel Syndrome (IBS) and Hirschsprung's disease, shedding light on the complex regulatory network underlying defecation.
正常的胃肠（GI）蠕动，包括排便，对于从昆虫到人类等各种物种的营养吸收、能量平衡和整体健康至关重要。胃肠蠕动的紊乱会导致便秘等情况或严重疾病。已知包括TRP通道和Piezo在内的机械传感器在调节黑腹果蝇的肠道生理中起关键作用，但它们在排便中的具体作用尚未完全了解。此外，像利尿激素44（DH44）这样的神经肽也与肠道调节有关。本研究使用基因敲除突变体和RNA干扰技术，探索了Trpγ、利尿激素44受体2（DH44R2）和Piezo在控制摄食量、肠道蠕动和排便方面的作用。这些基因的突变体表现出排泄物产量增加和体积增大，而Dh44和Dh44R1突变体的排泄物数量减少，但体积增大。共表达和拯救实验进一步证实了这些基因在同一肠道细胞中的关键作用。研究结果表明，局部肠道特异性机制是排便的主要驱动因素。这些结果突出了Trpγ、Piezo和DH44R2在调节肠道蠕动和排便方面的协同作用。通过揭示这些机械感觉蛋白和细胞如何共同发挥作用，这项研究可能为肠易激综合征（IBS）和先天性巨结肠等人类胃肠疾病提供见解，揭示排便背后复杂的调节网络。
