Journal article

The Anti-fibrotic Actions of Relaxin Are Mediated Through a NO-sGC-cGMP-Dependent Pathway in Renal Myofibroblasts In Vitro and Enhanced by the NO Donor, Diethylamine NONOate

Chao Wang, Barbara K Kemp-Harper, Martina Kocan, Sheng Yu Ang, Tim D Hewitson, Chrishan S Samuel



INTRODUCTION: The anti-fibrotic hormone, relaxin, has been inferred to disrupt transforming growth factor (TGF)-β1/Smad2 phosphorylation (pSmad2) signal transduction and promote collagen-degrading gelatinase activity via a nitric oxide (NO)-dependent pathway. Here, we determined the extent to which NO, soluble guanylate cyclase (sGC) and cyclic guanosine monophosphate (cGMP) were directly involved in the anti-fibrotic actions of relaxin using a selective NO scavenger and sGC inhibitor, and comparing and combining relaxin's effects with that of an NO donor. METHODS AND RESULTS: Primary renal cortical myofibroblasts isolated from injured rat kidneys were treated with human recombinant relaxin ..

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

Awarded by NHMRC Senior Research Fellowship

Funding Acknowledgements

We sincerely thank Corthera Inc (San Carlos, CA, USA; a subsidiary of Novartis AG, Basel, Switzerland) for providing the human recombinant relaxin used in this study. This study was supported by a National Health and Medical Research Council (NHMRC) of Australia Project Grant (GNT628634) to CS and TH, and by a NHMRC Senior Research Fellowship (GNT1041766) to CS.