INICSA   23916
INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Testosterone favors Smooth Muscle Cells Differentiation through Serum Response Factor/Myocardin (SRF/Myocd)
Autor/es:
CAROLINA LEIMGRUBER,NAHUEL PEINETTI, JOSEPH M.MIANO, CRISTINA A. MALDONADO; AMADO A. QUINTAR
Reunión:
Congreso; 12th International Congress of Cell Biology; 2016
Resumen:
It has been suggested that androgens exert differentiating effects on smooth muscle cells (SMCs) but the mechanisms remain still unknown. SMC myodifferentiation is controlled by the SRF/MYOCD complex in cardiac and vascular smooth muscle, with little information in others sites. Our aim was to analyze if SRF/MYOCD is involved in prostatic SMC differentiation and to determine the role of testosterone on SMC phenotype. Testosterone (10-12 to 10-5 M for 24h) up-regulated Srf/Myocd mRNA in primary cultures of prostatic SMCs in a dose-dependent manner, correlated with the increase of the SMC-specific genes Acta2, Cnn1 and Lmod1 and the decrease in the mesenchymal marker Vim. The inhibition of Myocd or Srf by transfecting SMCs with specific siRNAs avoided the myodifferentiating effects of testosterone.On the other hand, prostatic SMCs were treated with the endotoxin LPS 1ug/ml for 48h, resulting in a down-regulation of Srf/Myocd and leading to a dedifferentiated phenotype (characterized by decreased mRNA and protein levels of Acta2 and Cnn1 and increased Vim compared to controls). Electron microscopy corroborated the loss of the contractile status, with the development of a secretory profile after LPS treatment. To gain insight into the involvement of Myocd in SMC dedifferentiation under this proinflammatory conditions, the HCASM cell line was transduced with adenovirus carrying Myocd and then treated with LPS or TNF for 48h as dedifferentiator stimuli. The overexpression of Myocd resulted in a significant induction in Acta2, Cnn1, and Lmod1 mRNA expression, with no significant differences being found in the these markers when these cells were stimulated with LPS or TNF.Finally, prostatic SMCs were challenged by LPS for 48h and then treated with testosterone for additional 48h, with the androgen being able to restore the muscular phenotype by normalizing Srf/Myocd mRNA levels.These results provide novel evidence regarding the differentiating role of testosterone on SMCs by modulating Srf/Myocd, highlighting that androgens preserve prostatic SMC phenotype, which is essential to maintain the normal structure and function of the prostate.