title: The nuclear receptor NOR-1 regulates the small muscle protein, X-linked (SMPX) and myotube differentiation.
abstract: Recent works have highlighted the role of NOR-1 in both smooth and skeletal muscle, and have proposed this nuclear receptor as a nexus that coordinates muscle performance and metabolic capacity. However, no muscle specific genes regulated by NOR-1 have been identified so far. To identify NOR-1 target genes, we over-expressed NOR-1 in human vascular smooth muscle cells (VSMC). These cells subjected to sustained over-expression of supraphysiological levels of NOR-1 experienced marked phenotypic changes and up-regulated the skeletal muscle protein X-linked (SMPX), a protein typically expressed in striated muscle and associated to cell shape. By transcriptional studies and DNA-protein binding assays, we identified a non-consensus NBRE site in human SMPX promoter, critical for NOR-1 responsiveness. The expression of SMPX was higher in human skeletal muscle myoblasts (HSMM) than in human VSMC, and further increased in HSMM differentiated to myotubes. NOR-1 silencing prevented SMPX expression in HSMM, as well as their differentiation to myotubes, but the up-regulation of SMPX was dispensable for HSMM differentiation. Our results indicate that NOR-1 regulate SMPX in human muscle cells and acts as a muscle regulatory factor, but further studies are required to unravel its role in muscle differentiation and hypertrophy.
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ferrán
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Martí-Pàmies
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Alonso
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodríguez-Calvo
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Aguiló
authors.affiliation: Unitat de Diagnòstic i Teràpia Molecular, Banc de Sang i Teixits, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vidal
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, IIB-Sant Pau, c/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Martínez-González
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D026901:Membrane Transport Proteins; D009124:Muscle Proteins; C479458:OSCP1 protein, human; C433890:SMPX protein, human