AI Article Synopsis
- Diabetic nephropathy is a leading cause of renal failure and this study focused on the effects of hepatocyte growth factor (HGF) in advanced stages using a rat model of diabetes.
- Early-stage diabetic nephropathy displayed characteristics such as hyperfiltration and albuminuria, while advanced stages showed significant upregulation of TGF-beta1 and structural damage.
- The HGF gene therapy improved conditions in advanced diabetic nephropathy by reducing kidney damage markers, but had no positive effects in the early stage, indicating its potential as a treatment strategy for later stages of the disease.
Article 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.
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| http://dx.doi.org/10.2337/diabetes.53.4.1119 | DOI Listing |
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