Journal article

Relaxin Signals through a RXFP1-pERK-nNOS-NO-cGMP-Dependent Pathway to Up-Regulate Matrix Metalloproteinases: The Additional Involvement of iNOS

Bryna Suet Man Chow, Elaine Guo Yan Chew, Chongxin Zhao, Ross AD Bathgate, Tim D Hewitson, Chrishan S Samuel



The hormone, relaxin, inhibits aberrant myofibroblast differentiation and collagen deposition by disrupting the TGF-β1/Smad2 axis, via its cognate receptor, Relaxin Family Peptide Receptor 1 (RXFP1), extracellular signal-regulated kinase (ERK)1/2 phosphorylation (pERK) and a neuronal nitric oxide (NO) synthase (nNOS)-NO-cyclic guanosine monophosphate (cGMP)-dependent pathway. However, the signalling pathways involved in its additional ability to increase matrix metalloproteinase (MMP) expression and activity remain unknown. This study investigated the extent to which the NO pathway was involved in human gene-2 (H2) relaxin's ability to positively regulate MMP-1 and its rodent orthologue, MMP..

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

Funding Acknowledgements

This study was supported by a National Health and Medical Research Council of Australia (NHMRC) Project Grant (628634) to Chrishan S. Samuel and Tim D. Hewitson; a NHMRC Senior Research Fellowship to Ross A. D. Bathgate; a National Heart Foundation of Australia/NHMRC R. D. Wright Fellowship to Chrishan S. Samuel; and by the Victorian Government's Operational Infrastructure Support Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.