Involvement of HPSE in renal fibrosis. Several factors (high glucose concentrations, ROS, AGE) can increase HPSE production in both glomerular and tubular cells. The same factors induce cathepsin-l production by renal tubular cells, and this activates HPSE. Then the active HPSE can sustain inflammation by activating macrophages recruited from the circulation. During stress conditions both tubular and inflammatory cells release FGF-2 and TGF-β that, thanks to the higher amounts of HPSE, may activate the intracellular machinery leading to EMT.