Adhesion G Protein-Coupled Receptor () Expression Profiling in Diseased Mouse, Rat, and Human Kidneys.

Uncovering the function of understudied G protein-coupled receptors (GPCRs) provides a wealth of untapped therapeutic potential. The poorly understood adhesion GPCR () is widely expressed in developing kidneys. In adulthood, expression is enriched in parietal epithelial cells (PECs) and epithelial cells of the collecting duct and urothelium. Whether Gpr126 plays a role in kidney disease remains unclear. Here, we characterized expression in diseased kidneys in mice, rats, and humans. RT-PCR data show that expression is altered in kidney disease. A quantitative RNAscope analysis utilizing cell type-specific markers revealed that expression upon tubular damage is mainly increased in cell types expressing under healthy conditions as well as in cells of the distal and proximal tubules. Upon glomerular damage, an increase was mainly detected in PECs. Notably, expression was upregulated in an ischemia/reperfusion model within hours, while upregulation in a glomerular damage model was only detected after weeks. An analysis of kidney microarray data from patients with lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), hypertension, and diabetes as well as single-cell RNA-seq data from kidneys of patients with acute kidney injury and chronic kidney disease indicates that expression is also altered in human kidney disease. In patients with FSGS, an RNAscope analysis showed that mRNA is upregulated in PECs belonging to FSGS lesions and proximal tubules. Collectively, we provide detailed insights into expression in kidney disease, indicating that GPR126 is a potential therapeutic target.