AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

Bryna SM Chow; Martina Kocan; Matthew Shen; Yan Wang; Lei Han; Jacqueline Y Chew; Chao Wang; Sanja Bosnyak; Katrina M Mirabito-Colafella; Giannie Barsha; Belinda Wigg; Elizabeth KM Johnstone; Mohammed A Hossain; Kevin DG Pfleger; Kate M Denton; Robert E Widdop; Roger J Summers; Ross AD Bathgate; Tim D Hewitson; Chrishan S Samuel

Journal article

AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

Bryna SM Chow, Martina Kocan, Matthew Shen, Yan Wang, Lei Han, Jacqueline Y Chew, Chao Wang, Sanja Bosnyak, Katrina M Mirabito-Colafella, Giannie Barsha, Belinda Wigg, Elizabeth KM Johnstone, Mohammed A Hossain, Kevin DG Pfleger, Kate M Denton, Robert E Widdop, Roger J Summers, Ross AD Bathgate, Tim D Hewitson, Chrishan S Samuel

Journal of the American Society of Nephrology | AMER SOC NEPHROLOGY | Published : 2019

DOI: 10.1681/ASN.2019060597

Abstract

BACKGROUND: Recombinant human relaxin-2 (serelaxin), which has organ-protective actions mediated via its cognate G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1), has emerged as a potential agent to treat fibrosis. Studies have shown that serelaxin requires the angiotensin II (AngII) type 2 receptor (AT2R) to ameliorate renal fibrogenesis in vitro and in vivo. Whether its antifibrotic actions are affected by modulation of the AngII type 1 receptor (AT1R), which is expressed on myofibroblasts along with RXFP1 and AT2R, is unknown. METHODS: We examined the signal transduction mechanisms of serelaxin when applied to primary rat renal and human cardiac myofibroblasts in vitro..

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University of Melbourne Researchers

Timothy Hewitson Author Medicine - Royal Melbourne Hospital

Akhter Hossain Author Florey Department of Neuroscience and Mental Health

Chrishan Samuel Author Biochemistry and Pharmacology

Ross Bathgate Author Florey Department of Neuroscience and Mental Health

Martina Kocan Author Florey Department of Neuroscience and Mental Health

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC) project

Awarded by NHMRC

Awarded by NHMRC RD Wright Fellowship

Funding Acknowledgements

This study was supported by a University of Melbourne Fee Remission Scholarship to Dr. Chow; Australian Postgraduate Scholarships to Mr. Shen, Ms. Y. Wang, and Ms. Barsha; Monash University International Scholarship to Mr. C. Wang; National Health and Medical Research Council of Australia (NHMRC) project grants GNT0436713, GNT0454375, GNT0628634, GNT1045848, and GNT1101552; an NHMRC program grant (GNT1055134) to Prof. Summers; NHMRC Senior Research Fellowships to Prof. Bathgate (GNT1042650), Prof. Denton (GNT1041844), and Associate Prof. Samuel (GNT1041766); and an NHMRC RD Wright Fellowship to Associate Prof. Pfleger (GNT1085842). Research conducted at the Florey Institute of Neuroscience and Mental Health was additionally supported by the Victorian Government's Operational Infrastructure Support Program.