VDR y P38 MAPK están involucrados en la modulación de la miogénesis por el 1alpha,25(OH)2-vitamina D3 en células de músculo esquelético.

A. PAULA IRAZOQUI; HEIM NADIA; BOLAND RICARDO; BUITRAGO C

Buenos Aires

Congreso; XXXI Reunión Anual Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2014

Asociación Argentina de Osteología y Metabolismo Mineral

We previously reported that the VDR participates in cell proliferation and differentiation events triggered by 1,25(OH)2-vitamin D3 [1,25D] in C2C12 skeletal muscle cells. Specifically, studies in the past year demonstrated that 1,25D promotes the expression of cyclin D3 and cyclin dependent kinases (CDKs) inhibitors in a VDR-dependent manner. In this work we present data indicating that p38 MAPK is also involved in the mechanism by which 1,25D stimulates myogenesis. p38 MAPK activity was inhibited by pre-treatment of C2C12 cells with compound SB203580. Cell cycle studies by flow cytometry using propidium iodide staining evidenced that hormone treatment induced an arrest in the G0/G1 phase, effect which was dependent on p38 MAPK activation. The up-regulation of cyclin D3 by 1,25D was abolished in presence of SB203580. It was detected in parallel a 1,25D ?dependent acute increase in myogenin expression only when p38 MAPK was active, implying that the G0/G1 arrest was a pro-differentiating event where p38 MAPK is required. In agreement with these observations, p38 MAPK was also involved in the hormone -dependent augmented expression of the CDKs inhibitors p21Waf1/Cip1 and p27Kip1 in C2C12 wild type cells. Of relevance, p38 MAPK was shown to participate in the increase of VDR induced by 1,25D. The results indicate that p38 MAPK is involved in the control of the cellular cycle by 1,25D in skeletal muscle cells, sustaining the operation of a VDR and p38 MAPK ?dependent mechanism in hormone modulation of myogenesis.