Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis
Bryna S Man Chow, Martina Kocan, Sanja Bosnyak, Mohsin Sarwar, Belinda Wigg, Emma S Jones, Robert E Widdop, Roger J Summers, Ross AD Bathgate, Tim D Hewitson, Chrishan S Samuel
KIDNEY INTERNATIONAL | ELSEVIER SCIENCE INC | Published : 2014
Fibrosis is a hallmark of chronic kidney disease, for which there is currently no effective cure. The hormone relaxin is emerging as an effective antifibrotic therapy; however, its mechanism of action is poorly understood. Recent studies have shown that relaxin disrupts the profibrotic actions of transforming growth factor-β1 (TGF-β1) by its cognate receptor, relaxin family peptide receptor 1 (RXFP1), extracellular signal-regulated kinase phosphorylation, and a neuronal nitric oxide synthase-dependent pathway to abrogate Smad2 phosphorylation. Since angiotensin II also inhibits TGF-β1 activity through its AT2 receptor (AT2R), we investigated the extent to which relaxin interacts with the AT2..View full abstract
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
We thank Ms Chongxin Zhao for technical support. We are grateful to Professor Lutz Hein (University of Freiburg, Germany) for providing the AT<INF>2</INF>R knockout mice; A/Professor Kevin Pfleger (Western Australian Institute for Medical Research, Perth, WA, Australia), Drs Andreas Loening and Sanjiv Gambhir (Stanford University, Palo Alto, CA), and Dr Atsushi Miyawaki (RIKEN Brain Science Institute, Wakocity, Japan) for providing cDNA constructs (for the BRET assays); and Professor Walter Thomas (University of Queensland) for providing the HEK293 cells stably transfected with AT<INF>2</INF>Rs. This study was supported by a University of Melbourne Fee Remission Scholarship to BSMC; an Australian Research Council Postgraduate Scholarship to MS; National Health and Medical Research Council of Australia (NHMRC) Project Grants 436713, 454375, 628634, and APP1045848; NHMRC Senior Research Fellowships to RADB and CSS; a Monash University Mid-Career Fellowship to CSS; and by the Victorian Government's Operational Infrastructure Support Program.