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MCAM knockdown impairs PPARγ expression and 3T3-L1 fibroblasts differentiation to adipocytes

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Abstract

We investigated for the first time the expression of melanoma cell adhesion molecule (MCAM) and its involvement in the differentiation of 3T3-L1 fibroblasts to adipocytes. We found that MCAM mRNA increased subsequent to the activation of the master regulator of adipogenesis, PPARγ, and this increase was maintained in the mature adipocytes. On the other hand, MCAM knockdown impaired differentiation and induction of PPARγ as well as expression of genes activated by PPARγ. However, events that precede and are necessary for early PPARγ activation, such as C/EBPβ induction, β-catenin downregulation, and ERK activation, were not affected in the MCAM knockdown cells. In keeping with this, the increase in PPARγ mRNA that precedes MCAM induction was not altered in the knockdown cells. In conclusion, our findings suggest that MCAM is a gene upregulated and involved in maintaining PPARγ induction in the late but not in the early stages of 3T3-L1 fibroblasts adipogenesis.

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Acknowledgements

This work was supported by research grants from Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina (PIP0291), Agencia Nacional de Promoción Científica y Tecnológica of Argentina (PICT 2008-1826), and National Institutes of Health (R21 DK-113500, DGR). The funders had no role in study design, data analysis, decision to publish, or preparation of the manuscript. We thank J. Brandani for plasmids, A. Lago-Huvelle for help with immunofluorescence microscopy, and L. Barcos and F. Coluccio-Leskow for help with lentivirus production.

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Authors and Affiliations

  1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, 1428, Buenos Aires, Argentina

    Matías Gabrielli, Claudia N. Martini, Laura Judith Raiger Iustman & María del C. Vila

  2. Universidad de Buenos Aires, CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina

    Matías Gabrielli, Laura Judith Raiger Iustman & María del C. Vila

  3. Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    Damián G. Romero

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  1. Matías Gabrielli
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Correspondence to María del C. Vila.

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Gabrielli, M., Romero, D.G., Martini, C.N. et al. MCAM knockdown impairs PPARγ expression and 3T3-L1 fibroblasts differentiation to adipocytes. Mol Cell Biochem 448, 299–309 (2018). https://doi.org/10.1007/s11010-018-3334-8

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