Journal article

The anti-fibrotic actions of relaxin are mediated through AT(2)R-associated protein phosphatases via RXFP1-AT(2)R functional crosstalk in human cardiac myofibroblasts

Chao Wang, Anita A Pinar, Robert E Widdop, Mohammed A Hossain, Ross AD Bathgate, Kate M Denton, Barbara K Kemp-Harper, Chrishan S Samuel

The FASEB Journal | WILEY | Published : 2020

Abstract

Fibrosis is a hallmark of several cardiovascular diseases. The relaxin family peptide receptor 1 (RXFP1) agonist, relaxin, has rapidly occurring anti-fibrotic actions which are mediated through RXFP1 and angiotensin II receptor crosstalk on renal and cardiac myofibroblasts. Here, we investigated whether this would allow relaxin to indirectly activate angiotensin II type 2 receptor (AT2 R)-specific signal transduction in primary human cardiac myofibroblasts (HCMFs). The anti-fibrotic effects of recombinant human relaxin (RLX; 16.8 nM) or the AT2 R-agonist, Compound 21 (C21; 1 μM), were evaluated in TGF-β1-stimulated HCMFs, in the absence or presence of an RXFP1 antagonist (1 μM) or AT2 R anta..

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Grants

Awarded by Department of Health \ National Health and Medical Research Council (NHMRC)


Funding Acknowledgements

Department of Health vertical bar National Health and Medical Research Council (NHMRC), Grant/Award Number: GNT1101552, GNT1100676, GNT1135837, GNT1136813 and GNT1041766