Figure 7.

Targeting the urokinase plasminogen activator receptor (uPAR) pathway leads to attenuation of wound repair via different mechanisms. Urokinase plasminogen activator (uPA) binding to uPAR activates both extracellular and intracellular signalling cascades. (A) Plasminogen activator inhibitor 1 (PAI-1) binding to uPAR and its co-receptors interferes with signalling via multiple mechanisms. Damage to the epithelial layer leads to increased soluble uPAR (suPAR) and phosphorylation of Erk1/2 and p38. (B) Blocking the interaction between uPA and uPAR at the time of damage leads to decreased suPAR, uPA and PAI-1 in the supernatant, changes in activation of signalling pathways and attenuation of wound repair. (C) Increased levels of uPAR lead to increased receptor shedding, changes in matrix metalloproteinase 9 (MMP-9) activity and attenuation of wound repair. Soluble uPAR sequesters uPA and prevents it binding to cell surface uPAR.