Figure 2.

Molecular mechanisms by which p38 regulates the expression of MMPs, αSMA and IL-6 in cardiac fibroblasts. The p38 pathway is important for upregulating the expression of specific proteins in cardiac fibroblasts, including matrix metalloproteinases (MMPs), α-smooth muscle actin (αSMA/ACTA2) and interleukin-6 (IL-6). Modulation occurs at multiple levels, including the regulation of gene transcription and mRNA stability. P38 activation leads to phosphorylation and activation of specific transcription factors (via both direct and indirect mechanisms), and can also increase stability of specific mRNAs through the phosphorylation of mRNA stabilizing factors (e.g., HuR) and mRNA destabilizing factors (e.g., TTP). See main text for more details.