Figure 6. Schematic model of miR-143 and MAP2K5 regulation during ADSC adipogenesis.

(A) ERK5, as the substrate of MAP2K5, triggers clonal expansion and activates C/EBP-α, a pleiotropic transactivator of numerous adipocyte-specific genes that contribute to terminal differentiation. Thus, the overexpression of miR-143 in this phase blocks the clonal expansion stage and then terminal differentiation by inhibiting MAP2K5. However, blocking MAP2K5-ERK5 signaling pathway by inhibiting MAP2K5 during terminal differentiation stage reduces phosphorylation of PPAR-γ and thus promotes adipogenic differentiation. (B) Protein levels of MAP2K5 during ADSC differentiation were evaluated by western blot analysis at the indicated time points after the ADSCs were treated with MDI. (C) Induction of adipocyte differentiation with MDI initially resulted in cell growth and clonal expansion, which require MAP2K5 expression and miR-143 downregulation. However, when the cells switch from clonal expansion to the growth-arrest and terminal differentiation stages, MAP2K5 expression must be inhibited, so the expression of miR-143 increases.