Articles producció científica> Medicina i Cirurgia

FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway

  • Identification data

    Identifier: imarina:6387710
    Authors:
    Girona JRosales RPlana NSaavedra PMasana LVallvé J
    Abstract:
    Purpose: The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). Methods and Results: A DNA 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 μM) and PD98059 (10 μM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. Conclusions: These findings indicate a direct effect of FABP4 on the migration and prolifera
  • Others:

    Author, as appears in the article.: Girona J; Rosales R; Plana N; Saavedra P; Masana L; Vallvé J
    Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
    URV's Author/s: Girona Tell, Josefa / Masana Marín, Luis / Plana Gil, Núria / ROSALES RIBAS, ROSER / SAAVEDRA GARCIA, PAULA
    Abstract: Purpose: The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). Methods and Results: A DNA 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 μM) and PD98059 (10 μM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. Conclusions: These findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs. © 2013 Girona et al.
    Thematic Areas: Zootecnia / recursos pesqueiros Sociology Sociología Serviço social Saúde coletiva Química Psychology Psicología Planejamento urbano e regional / demografia Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Linguística e literatura Letras / linguística Interdisciplinary research in the social sciences Interdisciplinar Human geography and urban studies History & philosophy of science Historia Geografía Geociências General medicine General biochemistry,genetics and molecular biology General agricultural and biological sciences Farmacia Environmental studies Ensino Engenharias iv Engenharias iii Engenharias ii Engenharias i Enfermagem Educação física Educação Economia Direito Demography Comunicação e informação Ciências sociais aplicadas i Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência política e relações internacionais Ciência de alimentos Ciência da computação Biotecnología Biology Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Astronomia / física Arquitetura, urbanismo e design Archaeology Antropologia / arqueologia Anthropology Agricultural and biological sciences (miscellaneous) Administração, ciências contábeis e turismo Administração pública e de empresas, ciências contábeis e turismo
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 19326203
    Author's mail: josefa.girona@urv.cat nuria.plana@urv.cat luis.masana@urv.cat josefa.girona@urv.cat
    Author identifier: 0000-0002-6267-8779 0000-0002-4231-7618 0000-0002-0789-4954 0000-0002-6267-8779
    Record's date: 2023-02-26
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081914
    Papper original source: Plos One. 8 (11): e81914-
    APA: Girona J; Rosales R; Plana N; Saavedra P; Masana L; Vallvé J (2013). FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway. Plos One, 8(11), e81914-. DOI: 10.1371/journal.pone.0081914
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.1371/journal.pone.0081914
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2013
    Publication Type: Journal Publications
  • Keywords:

    Agricultural and Biological Sciences (Miscellaneous),Biochemistry, Genetics and Molecular Biology (Miscellaneous),Biology,Medicine (Miscellaneous),Multidisciplinary,Multidisciplinary Sciences
    Zootecnia / recursos pesqueiros
    Sociology
    Sociología
    Serviço social
    Saúde coletiva
    Química
    Psychology
    Psicología
    Planejamento urbano e regional / demografia
    Odontología
    Nutrição
    Multidisciplinary sciences
    Multidisciplinary
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Matemática / probabilidade e estatística
    Linguística e literatura
    Letras / linguística
    Interdisciplinary research in the social sciences
    Interdisciplinar
    Human geography and urban studies
    History & philosophy of science
    Historia
    Geografía
    Geociências
    General medicine
    General biochemistry,genetics and molecular biology
    General agricultural and biological sciences
    Farmacia
    Environmental studies
    Ensino
    Engenharias iv
    Engenharias iii
    Engenharias ii
    Engenharias i
    Enfermagem
    Educação física
    Educação
    Economia
    Direito
    Demography
    Comunicação e informação
    Ciências sociais aplicadas i
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência política e relações internacionais
    Ciência de alimentos
    Ciência da computação
    Biotecnología
    Biology
    Biodiversidade
    Biochemistry, genetics and molecular biology (miscellaneous)
    Astronomia / física
    Arquitetura, urbanismo e design
    Archaeology
    Antropologia / arqueologia
    Anthropology
    Agricultural and biological sciences (miscellaneous)
    Administração, ciências contábeis e turismo
    Administração pública e de empresas, ciências contábeis e turismo
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