Dataset Information


GPRC5b Modulates Inflammatory Response in Glomerular Diseases via NF-?B Pathway.

ABSTRACT: BACKGROUND:Inflammatory processes play an important role in the pathogenesis of glomerulopathies. Finding novel ways to suppress glomerular inflammation may offer a new way to stop disease progression. However, the molecular mechanisms that initiate and drive inflammation in the glomerulus are still poorly understood. METHODS:We performed large-scale gene expression profiling of glomerulus-associated G protein-coupled receptors (GPCRs) to identify new potential therapeutic targets for glomerulopathies. The expression of Gprc5b in disease was analyzed using quantitative PCR and immunofluorescence, and by analyzing published microarray data sets. In vivo studies were carried out in a podocyte-specific Gprc5b knockout mouse line. Mechanistic studies were performed in cultured human podocytes. RESULTS:We identified an orphan GPCR, Gprc5b, as a novel gene highly enriched in podocytes that was significantly upregulated in common human glomerulopathies, including diabetic nephropathy, IgA nephropathy, and lupus nephritis. Similar upregulation of Gprc5b was detected in LPS-induced nephropathy in mice. Studies in podocyte-specific Gprc5b knockout mice showed that Gprc5b was not essential for normal development of the glomerular filtration barrier. However, knockout mice were partially protected from LPS-induced proteinuria and recruitment of inflammatory cells. Mechanistically, RNA sequencing in Gprc5b knockouts mice and experiments in cultured human podocytes showed that Gpr5cb regulated inflammatory response in podocytes via NF-?B signaling. CONCLUSIONS:GPRC5b is a novel podocyte-specific receptor that regulates inflammatory response in the glomerulus by modulating the NF-?B signaling pathway. Upregulation of Gprc5b in human glomerulopathies suggests that it may play a role in their pathogenesis.

PROVIDER: S-EPMC6727250 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC3272332 | BioStudies
| S-EPMC4867620 | BioStudies
2019-01-01 | S-EPMC6586875 | BioStudies
| S-EPMC4814194 | BioStudies
| S-EPMC8246268 | BioStudies
| S-EPMC5192948 | BioStudies
| S-EPMC5856817 | BioStudies
| S-EPMC6533758 | BioStudies
| S-EPMC6249220 | BioStudies
| S-EPMC4978041 | BioStudies