Figure 10. Schematic illustration of the signaling transduction pathway leading to tPA promotion of myofibroblast activation.

tPA binds to membrane receptor LRP-1, induces its tyrosine phosphorylation, which leads to the increased recruitment of β1 integrin and activates downstream ILK. Blockade of each and every step within this signaling circuit by multiple strategies (numbers 1–5) abolishes the fibrogenic effect of tPA on myofibroblast activation, whereas over-expression of ILK mimics tPA and promotes the TGF-β1–mediated myofibroblast activation (number 6).