Format

Send to

Choose Destination
J Am Soc Nephrol. 2018 Jun;29(6):1679-1689. doi: 10.1681/ASN.2017101135. Epub 2018 Apr 10.

Depletion of Gprc5a Promotes Development of Diabetic Nephropathy.

Author information

1
Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Center, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
2
Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, and.
3
Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; and.
4
Bioscience, Cardiovascular, Renal and Metabolic Diseases, Innovative Medicines Biotech Unit, AstraZeneca, Gothenburg, Sweden.
5
Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Center, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden; jaakko.patrakka@ki.se.

Abstract

Background Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression.Methods To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein-coupled receptors (GPCRs) using human glomeruli.Results 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. Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement membrane and activation of mesangial cells, which are two hallmark features of DN in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated increased albuminuria and more severe histologic changes after induction of diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF-β signaling and activation of the EGF receptor in cultured podocytes.Conclusions Gprc5a has an important role in the pathogenesis of DN, and further study of the podocyte-specific signaling activity of this protein is warranted.

KEYWORDS:

EGFR; TGF-beta; diabetic nephropathy; podocyte

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center