Transporting epithelia provide a protective barrier against pathogenic insults while allowing the controlled exchange of ions, solutes and water with the external environment. In invertebrates, these functions depend on formation and maintenance of 'tight' septate junctions (SJs). However, the mechanism by which SJs affect transport competence and tissue homeostasis, and how these are modulated by ageing, remain incompletely understood. Here, we demonstrate that the Drosophila renal (Malpighian) tubules undergo an age-dependent decline in secretory capacity, which correlates with mislocalisation of SJ proteins and progressive degeneration in cellular morphology and tissue homeostasis. Acute loss of the SJ protein Snakeskin in adult tubules induced progressive changes in cellular and tissue architecture, including altered expression and localisation of junctional proteins with concomitant loss of cell polarity and barrier integrity, demonstrating that compromised junctional integrity is sufficient to replicate these ageing-related phenotypes. Taken together, our work demonstrates a crucial link between epithelial barrier integrity, tubule transport competence, renal homeostasis and organismal viability, as well as providing novel insights into the mechanisms underpinning ageing and renal disease.

中文翻译：

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果蝇蛇皮突变体中连接完整性受损表型与年龄相关的肾功能障碍。

运输上皮细胞提供了抵御病原体侵害的保护屏障，同时允许与外部环境进行离子、溶质和水的受控交换。在无脊椎动物中，这些功能取决于“紧密”隔膜连接（SJ）的形成和维持。然而，SJ 影响转运能力和组织稳态的机制，以及这些机制如何通过衰老进行调节，仍不完全清楚。在这里，我们证明果蝇肾（马尔皮基）小管的分泌能力会经历年龄依赖性的下降，这与 SJ 蛋白的错误定位以及细胞形态和组织稳态的进行性退化有关。成体肾小管中 SJ 蛋白 Snakeskin 的急性缺失会引起细胞和组织结构的渐进性变化，包括连接蛋白表达和定位的改变，同时伴随着细胞极性和屏障完整性的丧失，这表明连接完整性受损足以复制这些与衰老相关的蛋白质。表型。总而言之，我们的工作证明了上皮屏障完整性、肾小管运输能力、肾脏稳态和机体活力之间的重要联系，并为衰老和肾脏疾病的机制提供了新的见解。