My NCBI | Sign In
RSS Settings
  • Search:

Display Settings:

Format

Send to:

Choose Destination

    FASEB J. 2009 Apr;23(4):1219-29. Epub 2008 Dec 10.

    Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and Smad2.

    Mookerjee I, Hewitson TD, Halls ML, Summers RJ, Mathai ML, Bathgate RA, Tregear GW, Samuel CS.

    Howard Florey Institute, University of Melbourne, Victoria, Australia.

    The hormone relaxin inhibits renal myofibroblast differentiation by interfering with TGF-beta1/Smad2 signaling. However, the pathways involved in the relaxin-TGF-beta1/Smad2 interaction remain unknown. This study investigated the signaling mechanisms by which human gene-2 (H2) relaxin regulates myofibroblast differentiation in vitro by examining its effects on mixed populations of fibroblasts and myofibroblasts propagated from injured rat kidneys. Cultures containing approximately 60-70% myofibroblasts were used to determine which relaxin receptors, G-proteins, and signaling pathways were involved in the H2 relaxin-mediated regulation of alpha-smooth muscle actin (alpha-SMA; a marker of myofibroblast differentiation). H2 relaxin only inhibited alpha-SMA immunostaining and collagen concentration in the presence of relaxin family peptide receptor 1 (RXFP1). H2 relaxin also induced a transient rise in cAMP in the presence of G(i/o) inhibition, and a sustained increase in extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. Furthermore, inhibition of neuronal nitric oxide synthase (nNOS), NO, and cGMP significantly blocked the inhibitory effects of relaxin on alpha-SMA and Smad2 phosphorylation, while the NO inhibitor, L-nitroarginine methyl ester (hydrochloride) (L-NAME) significantly blocked the inhibitory actions of relaxin on collagen concentration in vivo. These findings suggest that relaxin signals through RXFP1, and a nNOS-NO-cGMP-dependent pathway to inhibit Smad2 phosphorylation and interfere with TGF-beta1-mediated renal myofibroblast differentiation and collagen production.

    PMID: 19073841 [PubMed - indexed for MEDLINE]

    Publication Types, MeSH Terms, Substances

    Publication Types:

    MeSH Terms:

    Substances:

    LinkOut - more resources

    Full Text Sources:

    Molecular Biology Databases:

    Miscellaneous:

    Libraries:

    Supplemental Content

    Click here to read Click here to read Click here to read Click here to read

    Related articles

    All links from this record

    • Related Articles

      Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.

    • Compound (MeSH Keyword)

      PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

    • Gene

      Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.

    • Gene (GeneRIF)

      Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.

    • HomoloGene

      HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.

    • Nucleotide

      Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.

    • Nucleotide (RefSeq)

      NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.

    • Nucleotide (Weighted)

      Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.

    • Protein (RefSeq)

      NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.

    • Protein (Weighted)

      Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.

    • Substance (MeSH Keyword)

      PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

    • Taxonomy via GenBank

      Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).

    • UniGene

      UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.

    • Protein

      Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.

    • GEO Profiles

      Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.

    Recent activity