Occasion, the importance of heparanase Doripenem Doribax in the development of DN evaluated. Interestingly, all KO Mice HPSE not used in our experiments, proteinuria in response to STZ-induced diabetes develop, and urinary excretion of albumin remained at the same level as before the beginning of diabetes. However, it was more than five times the rate of urinary albumin excretion in M Mice in weight after STZ-induced diabetes detected. In addition, heparanase deficiency resulted in the improvement of the mesangial matrix production expansion, the infiltration of macrophages, tubulointerstitial fibrosis, and overexpression of TGF b in the kidney of diabetic M Nozzles against HPSE KO WT. to support a causal involvement of heparanase in DN our results show a lower degree of albuminuria in type 1 and type 2 diabetic M mice with inhibitors against heparanase SST0001 M treated treated with vehicle use. Improvement of albuminuria by SST0001 is a proof of concept for the inhibition of heparanase as a therapeutic approach relevant in DN and warrants further studies to identify the most effective dose and sharing plans SST0001 Administration for the treatment in the future translation into clinical settings. In addition, the Aufkl Tion of the molecular mechanism of induction and heparanase specific pathogenic effect in the diabetic kidney disease is very important Behandlungsmodalit effective for the implementation Th anti-heparanase in the future. We found that the transcription factor EGR1 mediates the overexpression of heparanase in the diabetic kidney. In accordance with the reactivity
t of glucose EGR1 already reported in other cell types, we have demonstrated dose-dependent Independent induction of EGR1 expression in kidney cells cultivated in vitro and in vivo diabetic nephropathy. Interestingly, EGR1 induce both suppress and the expression of heparanase in dependence Dependence on the type of tissue / cells, it has been shown to activate heparanase expression in T cells and breast carcinoma, prostate and c to inhibit ion, but heparanase transcription in melanoma and pancreatic cancer cells. Trans-activation studies with EGR1 expression vector with a reporter construct promoter heparanase co-transfected showed that acts in the kidney cells EGR1 to stimulate transcription heparanase. The same experimental parameters showed that the occupation of ChIP analysis are obtained Hte heparanase promoter by EGR1 in the presence of high glucose levels, the best the r Problem Of EGR1 in the induction of glucose-dependent Independent heparanase in the kidney. A RESTRICTIONS LIMITATION this study is that our results do not provide enough information about the exact mode of action of heparanase in the pathogenesis of DN. In the past it was generally accepted that the induction of glomerular Ren heparanase in diabetes may contribute to the progression of DN Haupt Chlich by the degradation of HS in the GBM. Results support the importance of integrity T in HS Permselektivit t of glomerular Are REN filtration rate of the appearance of massive proteinuria following the administration of the monoclonal anti-HS rats, an increased Hte Durchl Permeability after 2 GBM remove the HS and 3 decreased GBM HS in the human / experimental diabetes, which correlates inversely with the degree of proteinuria. However, the effect of the residence GBM HS.