Emerging roles of renal intercalated cells

肾闰细胞的新作用

• 批准号: RGPIN-2017-06432
• 负责人: Cordat, Emmanuelle
• 金额: $ 1.89万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681476
• 关键词: Emerging; roles; renal; intercalated; cells

The kidney is a complex organ due to the “in series” organization of its various tubular segments. The collecting duct runs through the renal cortex (cortical collecting duct) and then the medulla (outer and inner medulla) prior to releasing final urine in the renal pelvis. It is composed of at least three different cell types: principal cells (PC), type-A and type-B intercalated cells (IC). While textbooks currently describe principal cells as mediating sodium and water reabsorption, and IC as responsible for acid-base homeostasis, recent in vivo findings support more versatile functions for these various cell types. We thus have to re-evaluate the function(s) of each cell type to normal renal physiology. ******Recent studies support that in addition to their acid-secreting function, type-A IC also play an essential role in innate immunity against uropathogenic E. coli (UPEC). Further, type-A IC in the outer medullary collecting duct can remodel into dendritic-like cells with lateral cytoplasmic projections, supporting that type-A IC may play more than just one role in acid-base homeostasis in renal physiology. However, at this time the intracellular and extracellular machinery that results in the cellular remodeling of IC's function to innate immunity is unknown. ******The long-term objective of this program is to decipher the multiple and complementary roles of intercalated and principal cell types in renal physiology. Our short-term objective is to dissect the cellular mechanisms that regulate the role IC play in normal renal physiology, in particular in innate immunity. This program has no conceptual or budgetary overlap with our currently funded research and is an independent research arm that we aim to develop in the next decade. Using cell biology and biochemical approaches on immortalized cell models of medullary IC, we will identify the UPEC attachment site to IC, and dissect the resulting intracellular signalling pathway(s), the hormonal regulation and cellular remodelling that lead to IC-mediated renal protection. Results from this program will contribute to a better understanding of the role(s) of IC in renal physiology and immunity.**

肾脏是一个复杂的器官，因为其各个管状部分是“串联”组织的。集合管穿过肾皮质（皮质集合管），然后穿过髓质（外髓质和内髓质），然后在肾盂中释放最终尿液。它由至少三种不同的细胞类型组成：主细胞 (PC)、A 型和 B 型闰细胞 (IC)。虽然教科书目前将主细胞描述为介导钠和水的重吸收，而 IC 负责酸碱稳态，但最近的体内研究结果支持这些不同细胞类型具有更通用的功能。因此，我们必须重新评估每种细胞类型对正常肾脏生理的功能。 ******最近的研究表明，除了其酸分泌功能外，A 型 IC 还在针对尿路致病性大肠杆菌 (UPEC) 的先天免疫中发挥着重要作用。此外，外髓集合管中的 A 型 IC 可以重塑为具有侧向细胞质投射的树突状细胞，这支持 A 型 IC 在肾脏生理学中的酸碱稳态中可能不仅仅发挥一种作用。然而，目前导致 IC 功能对先天免疫进行细胞重塑的细胞内和细胞外机制尚不清楚。 ******该计划的长期目标是破译插层细胞和主要细胞类型在肾脏生理学中的多重和互补作用。我们的短期目标是剖析调节 IC 在正常肾脏生理学中发挥作用的细胞机制，特别是在先天免疫中。该计划与我们目前资助的研究没有概念或预算重叠，是我们计划在未来十年发展的一个独立研究部门。在髓质 IC 的永生化细胞模型上使用细胞生物学和生化方法，我们将识别 IC 的 UPEC 附着位点，并剖析由此产生的细胞内信号通路、激素调节和细胞重塑，从而实现 IC 介导的肾脏保护。该计划的结果将有助于更好地了解 IC 在肾脏生理和免疫中的作用。**