Please use this identifier to cite or link to this item:
Title: Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats
Author: Cruzado, Josep Ma.
Lloberas Blanch, Núria
Torras Ambròs, Joan
Riera, Marta
Fillat i Fonts, Cristina
Herrero Fresneda, Immaculada
Aran Perramon, Josep M.
Alperovich, Gabriela
Vidal-Bel, August
Grinyó Boira, Josep M.
Keywords: Neuropaties diabètiques
Teràpia genètica
Factors de creixement
Diabetic neuropathies
Gene therapy
Growth factors
Issue Date: Apr-2004
Publisher: American Diabetes Association
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.
Note: Reproducció del document publicat a:
It is part of: Diabetes, 2004, vol. 53, num. 4, p. 1119-1127
Related resource:
ISSN: 0012-1797
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Medicina)

Files in This Item:
File Description SizeFormat 
531029.pdf1.59 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons