Figure 8.

Rescue of the aged fibroblast to myofibroblast differentiation by amplification of TGF-β signaling via the Tak1/AMPK/p38MAPK pathway. Stimulation of cardiac fibroblasts derived from young animals (Young) with TGF-β1 resulted in phosphorylation of Smad3 and increased expression of α-SMA (left panel). Cardiac fibroblasts derived from 30-month-old animals (Aged) demonstrated reduced expression of both TβRI and TβRII, which resulted in decreased signal transduction and diminished α-SMA expression (middle panel). AICAR/TGF-β1 synergistically activated Tak1, AMPK, and p38MAPK, resulting in up-regulation of α-SMA expression (right panel). Large and small font sizes indicate, respectively, up-regulation or reduction of expression.