Publications by authors named "Bryna S Man Chow"

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Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis.

Kidney Int 2014 Jul 15;86(1):75-85. Epub 2014 Jan 15.

1] Florey Institute of Neuroscience and Mental Health, Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia [2] Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia [3] Department of Pharmacology, Monash University, Clayton, VIC, Australia.

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 AT2R. The effects of the AT2R antagonist, PD123319, on relaxin activity were examined in primary rat kidney myofibroblasts, and in kidney tissue from relaxin-treated male wild-type and AT2R-knockout mice subjected to unilateral ureteric obstruction. Relaxin's antifibrotic actions were significantly blocked by PD123319 in vitro and in vivo, or when relaxin was administered to AT2R-knockout mice. While heterodimer complexes were formed between RXFP1 and AT2Rs independent of ligand binding, relaxin did not directly bind to AT2Rs but signaled through RXFP1-AT2R heterodimers to induce its antifibrotic actions. These findings highlight a hitherto unrecognized interaction that may be targeted to control fibrosis progression.
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http://dx.doi.org/10.1038/ki.2013.518DOI Listing
July 2014
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