IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MCAM KNOCKDOWN INHIBITS PPAR GAMMA EXPRESSION IN THE LATE STAGES OF 3T3-L1 FIBROBLASTS DIFFERENTIATION TO ADIPOCYTES
Autor/es:
CLAUDIA N. MARTINI; MATÍAS GABRIELLI; MARÍA DEL CARMEN VILA
Lugar:
Ciudad de Buenos Aires
Reunión:
Congreso; Reunion Conjunta de Sociedades de Biociencia; 2017
Resumen:
Obesity is a chronic disease characterized by an excessive expansion of the adipose tissue which is associated with an increase in the number and size of adipocytes. Therefore, the knowledge on the development and function of the adipose tissue may help to design new approaches for the treatment of this disease. We have previously observed that the expression of Melanoma Cell Adhesion Molecule (MCAM), a transmembrane protein of the immunoglobulin superfamily, increases during 3T3-L1 fibroblasts differentiation to adipocytes, subsequent to the activation of the master regulator of adipogenesis, PPARγ, and this increase is maintained in the mature adipocytes. On the other hand, we have also found that shRNA mediated MCAM downregulation impaired 3T3-L1 cells differentiation and induction of PPARγ as well as expression of genes activated by PPARγ. To further evaluate the effects of knocking down MCAM expression, we investigated the events that precede and are necessary for early PPARγ activation such as C/EBPβ induction, β-catenin downregulation and ERK activation. We found that these early events of the differentiation process were not affected in the MCAM knockdown cells. In keeping with this, the early increase in PPARγ mRNA observed 24 h after induction of differentiation and that precedes MCAM induction, was not altered in the knockdown cells. However, PPARγ expression was inhibited after day 3 of differentiation in these cells, when a positive feedback loop has been described to be necessary to maintain PPARγ upregulation. In conclusion, our findings suggest that MCAM is a gene upregulated and necessary to maintain PPARγ induction in the late but not in the early stages of 3T3-L1 fibroblasts adipogenesis.