Depletion of Gprc5a Promotes Development of Diabetic Nephropathy.

Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression. To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein-coupled receptors (GPCRs) using human glomeruli. We identified an orphan GPCR, Gprc5a, as a highly podocyte-specific gene, the expression of which was significantly downregulated in glomeruli of patients with DN compared with those without DN.

Confocal super-resolution imaging of the glomerular filtration barrier enabled by tissue expansion.

The glomerular filtration barrier, has historically only been spatially resolved using electron microscopy due to the nanometer-scale dimensions of these structures. Recently, it was shown that the nanoscale distribution of proteins in the slit diaphragm can be resolved by fluorescence based stimulated emission depletion microscopy, in combination with optical clearing. Fluorescence microscopy has advantages over electron microscopy in terms of multiplex imaging of different epitopes, and also the amount of volumetric data that can be extracted from thicker samples.