Bock Fabian, Li Shensen, Pozzi Ambra, Zent Roy
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Veterans Affairs Hospital, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Nat Rev Nephrol. 2025 Mar;21(3):157-174. doi: 10.1038/s41581-024-00906-1. Epub 2024 Dec 6.
The development and proper functioning of the kidney is dependent on the interaction of kidney cells with the surrounding extracellular matrix (ECM). These interactions are mediated by heterodimeric membrane-bound receptors called integrins, which bind to the ECM via their extracellular domain and via their cytoplasmic tail to intracellular adaptor proteins, to assemble large macromolecular adhesion complexes. These interactions enable integrins to control cellular functions such as intracellular signalling and organization of the actin cytoskeleton and are therefore crucial to organ function. The different nephron segments and the collecting duct system have unique morphologies, functions and ECM environments and are thus equipped with unique sets of integrins with distinct specificities for the ECM with which they interact. These cell-type-specific functions are facilitated by specific intracellular integrin binding proteins, which are critical in determining the integrin activation status, ligand-binding affinity and the type of ECM signals that are relayed to the intracellular structures. The spatiotemporal expression of integrins and their specific interactions with binding partners underlie the proper development, function and repair processes of the kidney. This Review summarizes our current understanding of how integrins, their binding partners and the actin cytoskeleton regulate kidney development, physiology and pathology.
肾脏的发育和正常功能依赖于肾细胞与周围细胞外基质（ECM）的相互作用。这些相互作用由称为整合素的异二聚体膜结合受体介导，整合素通过其细胞外结构域与ECM结合，并通过其细胞质尾部与细胞内衔接蛋白结合，以组装大型大分子黏附复合物。这些相互作用使整合素能够控制细胞功能，如细胞内信号传导和肌动蛋白细胞骨架的组织，因此对器官功能至关重要。不同的肾单位节段和集合管系统具有独特的形态、功能和ECM环境，因此配备了独特的整合素组合，它们对与之相互作用的ECM具有不同的特异性。这些细胞类型特异性功能由特定的细胞内整合素结合蛋白促进，这些蛋白对于确定整合素的激活状态、配体结合亲和力以及传递到细胞内结构的ECM信号类型至关重要。整合素的时空表达及其与结合伙伴的特异性相互作用是肾脏正常发育、功能和修复过程的基础。本综述总结了我们目前对整合素、其结合伙伴和肌动蛋白细胞骨架如何调节肾脏发育、生理学和病理学的理解。
