Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats. Export

@article{citeulike:3826214, abstract = {Diabetic nephropathy is the main cause of end-stage renal disease requiring dialysis in developed countries. In this study, we demonstrated the therapeutic effect of hepatocyte growth factor (HGF) on advanced rather than early diabetic nephropathy using a rat model of streptozotocin-induced diabetes. Early diabetic nephropathy (16 weeks after induction of diabetes) was characterized by albuminuria, hyperfiltration, and glomerular hypertrophy, whereas advanced diabetic nephropathy showed prominent transforming growth factor (TGF)-beta1 upregulation, mesangial expansion, and glomerulosclerosis. An SP1017-formulated human HGF (hHGF) plasmid was administered by intramuscular injection combined with electroporation over a 30-day follow-up in rats with early and advanced diabetic nephropathy. hHGF gene therapy upregulated endogenous rat HGF in the diabetic kidney (rat HGF by RT-PCR was threefold higher than in diabetic rats without therapy). hHGF gene therapy did not improve functional or morphologic abnormalities in early diabetic nephropathy. hHGF gene therapy reduced albuminuria and induced strong regression of mesangial expansion and glomerulosclerosis in advanced diabetic nephropathy. These findings were associated with suppression of renal TGF-beta1 and mesangial connective tissue growth factor (CTGF) upregulation, inhibition of renal tissue inhibitor of metalloproteinase (TIMP)-1 expression, and reduction of renal interstitial myofibroblasts. In conclusion, our results suggest that hHGF gene therapy may be considered as an innovative therapeutic strategy to treat advanced diabetic nephropathy.}, author = {Cruzado, Josep M. and Lloberas, N\'{u}ria and Torras, Joan and Riera, Marta and Fillat, Cristina and Herrero-Fresneda, Immaculada and Aran, Josep M. and Alperovich, Gabriela and Vidal, August and Griny\'{o}, Josep M.}, citeulike-article-id = {3826214}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/15047630}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=15047630}, issn = {0012-1797}, journal = {Diabetes}, keywords = {dn, gene-therapy, hgf, rat}, month = {April}, number = {4}, pages = {1119--1127}, posted-at = {2008-12-27 14:51:36}, priority = {2}, title = {Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/15047630}, volume = {53}, year = {2004} }

TY - JOUR ID - citeulike:3826214 L3 - citeulike-article-id:3826214 N2 - Diabetic nephropathy is the main cause of end-stage renal disease requiring dialysis in developed countries. In this study, we demonstrated the therapeutic effect of hepatocyte growth factor (HGF) on advanced rather than early diabetic nephropathy using a rat model of streptozotocin-induced diabetes. Early diabetic nephropathy (16 weeks after induction of diabetes) was characterized by albuminuria, hyperfiltration, and glomerular hypertrophy, whereas advanced diabetic nephropathy showed prominent transforming growth factor (TGF)-beta1 upregulation, mesangial expansion, and glomerulosclerosis. An SP1017-formulated human HGF (hHGF) plasmid was administered by intramuscular injection combined with electroporation over a 30-day follow-up in rats with early and advanced diabetic nephropathy. hHGF gene therapy upregulated endogenous rat HGF in the diabetic kidney (rat HGF by RT-PCR was threefold higher than in diabetic rats without therapy). hHGF gene therapy did not improve functional or morphologic abnormalities in early diabetic nephropathy. hHGF gene therapy reduced albuminuria and induced strong regression of mesangial expansion and glomerulosclerosis in advanced diabetic nephropathy. These findings were associated with suppression of renal TGF-beta1 and mesangial connective tissue growth factor (CTGF) upregulation, inhibition of renal tissue inhibitor of metalloproteinase (TIMP)-1 expression, and reduction of renal interstitial myofibroblasts. In conclusion, our results suggest that hHGF gene therapy may be considered as an innovative therapeutic strategy to treat advanced diabetic nephropathy. IS - 4 JF - Diabetes SN - 0012-1797 EP - 1127 TI - Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats. VL - 53 SP - 1119 KW - dn KW - gene-therapy KW - hgf KW - rat AU - Cruzado, Josep AU - Lloberas, Núria AU - Torras, Joan AU - Riera, Marta AU - Fillat, Cristina AU - Herrero-Fresneda, Immaculada AU - Aran, Josep AU - Alperovich, Gabriela AU - Vidal, August AU - Grinyó, Josep PY - 2004/04// UR - http://view.ncbi.nlm.nih.gov/pubmed/15047630 ER -