Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

Figure 1

A hypothesis for the pathogenesis of suPAR-mediated FSGS. suPAR is formed from various immune cells after cleavage of GPI anchor by cytokines such as TNF-α. suPAR can activate αvβ₃ integrin of podocytes. TNF-α can directly activate podocyte αvβ₃ integrin and vinculin. Another serum factors might decrease SMPDL3b in podocytes, causing αvβ₃ integrin activation through increased binding of suPAR/uPAR and αvβ₃ integrin. Cdc42 and Rac1 can be activated by uPAR-αvβ₃ integrin signaling and the podocyte actin cytoskeleton shifts from a stationary to a motile phenotype, thereby causing foot process effacement and proteinuria. uPAR-αvβ₃ integrin signaling in podocytes can be blocked through various pathways. NK, natural killer; uPAR, urokinase-type plasminogen activator receptor; suPAR, soluble urokinase-type plasminogen activator receptor; GPI, glycosylphosphatidylinositol; TNF, tumor necrosis factor; NFAT, nuclear factor of activated T cells; MMF, mycophenolate mofetil; GTP, guanosine-5′-triphosphate; SMPDL, sphingomyelin phosphodiesterase acid-like; ASMase, acid sphingomyelinase.