Renal cell markers: lighthouses for managing renal diseases

Abstract

Kidneys, one of the vital organs in our body, are responsible for maintaining whole body homeostasis. The complexity of renal function (e.g., filtration, reabsorption, fluid and electrolyte regulation, and urine production) demands diversity not only at the level of cell types but also in their overall distribution and structural framework within the kidney. To gain an in depth molecular-level understanding of the renal system, it is imperative to discern the components of kidney and the types of cells residing in each of the subregions. Recent developments in labeling, tracing, and imaging techniques have enabled us to mark, monitor, and identify these cells in vivo with high efficiency in a minimally invasive manner. In this review, we summarize different cell types, specific markers that are uniquely associated with those cell types, and their distribution in the kidney, which altogether make kidneys so special and different. Cellular sorting based on the presence of certain proteins on the cell surface allowed for the assignment of multiple markers for each cell type. However, different studies using different techniques have found contradictions in cell type-specific markers. Thus, the term "cell marker" might be imprecise and suboptimal, leading to uncertainty when interpreting the data. Therefore, we strongly believe that there is an unmet need to define the best cell markers for a cell type. Although the compendium of renal-selective marker proteins presented in this review is a resource that may be useful to researchers, we acknowledge that the list may not be necessarily exhaustive.

Keywords: Bowman’s capsule; glomerulus; kidney; nephron; podocytes; proximal tubules.

Graphical abstract

Figure 1.

Renal cell markers. Shown is a cartoon illustrating the spatial arrangement of a nephron with the various domains segmented and associated markers indicated in a box. The image is not drawn to scale. PDGFR, platelet-derived growth factor receptor; α-SMA, α-smooth muscle actin; TRPC, transient receptor potential canonical ion channel; eNOS, endothelial nitric oxide synthase; vWF, von Willebrand factor; PECAM-1, platelet endothelial cell adhesion molecule-1; NKCC2, Na⁺-K⁺-2Cl⁻ cotransporter; NXC1, Na⁺/Ca²⁺ exchanger isoform 1; FSP-1, fibroblast-specific protein 1; SCNN1, Na⁺ channel nonneuronal 1; Sca-1, stem cell antigen-1; NCC, Na⁺/Cl⁻ cotransporter; GLEPP1; glomerular epithelial protein 1; WT-1, Wilms’ tumor-1; CLIC5, Cl⁻ intracellular channel protein 5; CaSR, Ca²⁺-sensing receptor; NaS1, Na⁺-sulfate cotransporter; NaPi, type II Na⁺-coupled phosphate; AE1, anion exchanger 1; UT-A1, urea transporter A1.