HPSE and diabetic kidney disease: It was also shown that by regulating the bioavailability and activity of growth factors (FGF-2 and TGF-β), HPSE promotes tubular epithelial-to-mesenchymal transition (EMT) of proximal tubular cells and kidney fibrosis [30,31], and in streptozotocin-induced diabetic nephropathy model, HPSE-KO mice showed less interstitial fibrosis compared to untreated mice [32].