Fig. 3. Attenuation of p38 MAPK promotes expression of the myogenic phenotype. The normal increase in Col2a1 expression over time in primary cultures is blocked by SB202190, whereas myogenin, present at low levels early on, decreases in expression in the untreated cultures while continuing to increase in response to SB202190 (A). Mef2c is also more abundant in SB202190-treated cultures by day 3 compared with the untreated control (A). SB202190 causes a concentration-dependent decrease in the activity of a pGL3(4X48) reporter gene (B), whereas the activity of a transfected E-box-luciferase (pGL3-E4-Luc) reporter was increased in response to increasing concentrations of SB202190 (C). A modest increase was also observed in the activities of reporters containing the myogenin promoter (pGL3-myogenin-Luc) and the cardiac actin promoter (pGL3-c-actin-Luc) (C). When co-transfected with GAL4-MEF2A or GAL4-MEF2C, the activity of a GAL4 reporter (pG5-Luc) was enhanced by SB202190 (D). [ANOVAs (C-E) P<0.0001; Bonferroni post-tests, (C-E): #P<0.05, *P<.01, **P<0.001)].