Cell-cell crosstalk in kidney health and disease

Communication is fundamental to the function of complex multicellular organ systems, and it guides coordinated tissue responses in health and disease. In the kidney, various modalities of cell-cell crosstalk - including ligand-receptor interactions, direct cell-cell contact, cell-matrix connections and interactions with extracellular vesicles - are essential to the maintenance of organ and whole-body homeostasis. Dysregulation of any of these communication networks can lead to loss of kidney structure and function and culminate in kidney disease. Cell-cell crosstalk represents a complex, dynamic network of interactions that span multiple pathways and cell types. Glomerular VEGF signalling represents a prototypical example, whereby imbalanced communication between podocytes and glomerular endothelial cells can contribute to glomerular pathology. Other studies have highlighted the importance of angiogenic and anti-angiogenic signalling in the development of peritubular capillary rarefaction - a hallmark of progressive kidney disease. These examples underscore the mechanisms by which dysregulated crosstalk between specific kidney cell populations can contribute to disease pathogenesis across multiple compartments in the kidney. Novel technologies such as single-cell and spatial multi-omic platforms, integrated with advanced computational approaches, have enabled high-resolution mapping of cellular interactions and signalling networks, unlocking novel biological insights and therapeutic innovations.