Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.

Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a secreted proteoglycan, with notable expression in kidney, which attenuates inflammation and albuminuria. However, little is known about expression in mature tissues in the presence or absence of diabetes. We utilized publicly available single-cell RNA sequencing data to characterize expression in 27,786 renal endothelial cells (RECs) obtained from three mouse and four human databases. We validated our findings using bulk transcriptome data from 20 healthy subjects and 41 patients with DKD and using RNAscope. In both mice and humans, is expressed in a subset of all REC types and represents a minority of glomerular RECs. In patients, (+) cells exhibit conserved enrichment for blood vessel development genes. With diabetes, these cells are fewer in number and shift expression toward chemotaxis pathways. correlates with a majority of genes within these pathways, delineating a glomerular transcriptional polarization reflected by the magnitude of deficiency. Diabetes correlates with lower expression and with changes in the functional characterization of (+) cells. Thus, appears to be a marker for glomerular transcriptional polarization in DKD. Esm-1 is primarily expressed in glomerular endothelium in humans. Cells expressing exhibit a high degree of conservation in the enrichment of genes related to blood vessel development. In the context of diabetes, these cells are reduced in number and show a significant transcriptional shift toward the chemotaxis pathway. In diabetes, there is a transcriptional polarization in the glomerulus that is reflected by the degree of deficiency.