P38 MAPK and VDR are requiered in 1alpha,25(OH)2-vitamin D3-dependent cell cycle modulation in skeletal muscle cells.

ANA P. IRAZOQUI; CLAUDIA G. BUITRAGO; RICARDO L. BOLAND

Chicago, IL

Workshop; 17th Vitamin D Workshop; 2014

We previously reported that 1,25(OH)2-vitamin D3 (1,25D) induces rapid p38 MAPK activation in a VDR-dependent manner in proliferative C2C12 myoblast cells. Recently it was evidenced that VDR is required in the cell cycle modulation. We now present data indicating that p38 MAPK also participates in the mechanism by which the 1,25D mediates muscle cells proliferation and differentiation. In C2C12 cells, VDR was knocked down by a shRNA and p38 MAPK was successfully inhibited using SB-203580. The hormone prompts a peak of S-phase followed by an arrest in G0/G1-phase, evidenced by flow cytometry, which was dependent on p38 MAPK activation in wild type cells. Moreover, 1,25D induces an increase in cyclin D3, and CDK inhibitors, p21Waf1/Cip1 and p27Kip1, expression during G0/G1 arrest. In all these events, the activation of p38 MAPK was required. At the same time, a 1,25D?dependent acute increase in myogenin expression was observed when p38 MAPK was activated; indicating G0/G1 arrest of cells is a pro-differentiative event. In conclusion, VDR and p38 MAPK are involved in control of cellular cycle by 1,25D in skeletal muscle cells, providing key information on the mechanism underlying hormone regulation of myogenesis.