Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: The additional involvement of iNOS

BSM Chow; EGY Chew; C Zhao; RAD Bathgate; TD Hewitson; CS Samuel

Journal article

Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: The additional involvement of iNOS

BSM Chow, EGY Chew, C Zhao, RAD Bathgate, TD Hewitson, CS Samuel

Plos One | PUBLIC LIBRARY SCIENCE | Published : 2012

DOI: 10.1371/journal.pone.0042714

Download PDF

Abstract

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..

View full abstract

University of Melbourne Researchers

Ross Bathgate Author

Timothy Hewitson Author

Related Projects (2)

NHMRC RESEARCH FELLOWSHIP 2008 - BATHGATE

I am a molecular endocrinologist determining the mechanisms by which relaxin family peptides bind to and activate their receptors and induce..

Mechanisms of renal scarring

Fibrosis is a key cause of renal pathology-dysfunction. Relaxin is an endogenous reno-protective factor, and thus has enormous therapeutic p..

Grants

Awarded by Seventh Framework Programme

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.