To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

GPRC5b Modulates Inflamma… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

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

Journal article
Authors S. Zambrano
K. Moller-Hackbarth
X. D. Li
P. Q. Rodriguez
E. Charrin
A. Schwarz
Jenny Nyström
A. O. Wernerson
M. Lal
J. Patrakka
Published in Journal of the American Society of Nephrology
Volume 30
Issue 9
Pages 1573-1586
ISSN 1046-6673
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 1573-1586
Language en
Links dx.doi.org/10.1681/asn.2019010089
Keywords kidney, podocytes, nephrin, illuminate, ligands, murine, model, Urology & Nephrology
Subject categories Urology and Nephrology

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-kappa B signaling. Conclusions GPRC5b is a novel podocyte-specific receptor that regulates inflammatory response in the glomerulus by modulating the NF-kappa B signaling pathway. Upregulation of Gprc5b in human glomerulopathies suggests that it may play a role in their pathogenesis.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?