Journal
NATURE REVIEWS NEPHROLOGY
Volume 17, Issue 7, Pages 441-464Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41581-021-00411-9
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Funding
- Marie Sklodowska-Curie individual fellowship
- 'Fonds voor Wetenschappelijk Onderzoek' (FWO)
- Federal Government Belgium grant [IUAP P7/03]
- long-term structural Methusalem funding by the Flemish Government, FWO
- European Research Council (ERC) Advanced Research Grant [EU-ERC269073]
- RegMedXB
- Foundation Against Cancer
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Renal endothelial cells exhibit phenotypic and molecular heterogeneity in response to different microenvironments, supporting kidney functions and potentially serving as targets for therapeutic strategies. Understanding the diversity and specialization of kidney endothelial cells could offer new approaches for treating kidney diseases and promoting kidney regeneration.
The adult kidney vasculature comprises diverse populations of endothelial cells that support specific functions according to their microenvironment. This Review summarizes our current understanding of the phenotypic, molecular and metabolic heterogeneity of renal endothelial cells in relation to their microenvironment and the potential application of targeting renal endothelial cell metabolism as a therapeutic strategy for kidney diseases or kidney regeneration. Complex multicellular life in mammals relies on functional cooperation of different organs for the survival of the whole organism. The kidneys play a critical part in this process through the maintenance of fluid volume and composition homeostasis, which enables other organs to fulfil their tasks. The renal endothelium exhibits phenotypic and molecular traits that distinguish it from endothelia of other organs. Moreover, the adult kidney vasculature comprises diverse populations of mostly quiescent, but not metabolically inactive, endothelial cells (ECs) that reside within the kidney glomeruli, cortex and medulla. Each of these populations supports specific functions, for example, in the filtration of blood plasma, the reabsorption and secretion of water and solutes, and the concentration of urine. Transcriptional profiling of these diverse EC populations suggests they have adapted to local microenvironmental conditions (hypoxia, shear stress, hyperosmolarity), enabling them to support kidney functions. Exposure of ECs to microenvironment-derived angiogenic factors affects their metabolism, and sustains kidney development and homeostasis, whereas EC-derived angiocrine factors preserve distinct microenvironment niches. In the context of kidney disease, renal ECs show alteration in their metabolism and phenotype in response to pathological changes in the local microenvironment, further promoting kidney dysfunction. Understanding the diversity and specialization of kidney ECs could provide new avenues for the treatment of kidney diseases and kidney regeneration.
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