原创力文档relaxin signals through a rxfp1-perk-nnos-no-cgmp-dependent pathway to up-regulate matrix metalloproteinases the additional involvement of inos松弛素的信号通过rxfp1-perk-nnos-no-cgmp-dependent通路调控的基质金属蛋白酶伊诺的额外的参与.pdfVIP
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relaxin signals through a rxfp1-perk-nnos-no-cgmp-dependent pathway to up-regulate matrix metalloproteinases the additional involvement of inos松弛素的信号通过rxfp1-perk-nnos-no-cgmp-dependent通路调控的基质金属蛋白酶伊诺的额外的参与
Relaxin Signals through a RXFP1-pERK-nNOS-NO-cGMP-
Dependent Pathway to Up-Regulate Matrix
Metalloproteinases: The Additional Involvement of iNOS
1,2 1¤ 1 1,2
Bryna Suet Man Chow , Elaine Guo Yan Chew , Chongxin Zhao , Ross A. D. Bathgate ,
Tim D. Hewitson3,4*, Chrishan S. Samuel1,2,5*
1 Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria, Australia, 2 Department of Biochemistry and Molecular Biology, University of Melbourne,
Parkville, Victoria, Australia, 3 Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia, 4 Department of Medicine, University of Melbourne,
Royal Melbourne Hospital, Parkville, Victoria, Australia, 5 Department of Pharmacology, Monash University, Clayton, Victoria, Australia
Abstract
The hormone, relaxin, inhibits aberrant myofibroblast differentiation and collagen deposition by disrupting the TGF- b1/
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-13, MMP-2 and MMP-9
(the main collagen-degrading MMPs) in TGF-b1-stimulated human dermal fibroblasts and primary renal myofibroblasts
isolated from injured rats; by gelatin zymography (media) and Western blotti
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