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Imatinib attenuates diabetic nephropathy in apolipoprotein E-knockout mice
Markus Lassila1, Karin Jandeleit-Dahm, Kwee K Seah
1Baker Heart Research Institute, P.O. Box 6492, Commercial Road, Melbourne 8008, VIC 3004, Australia.
Journal of the American Society of Nephrology : JASN
|December 31, 2004
Summary
Platelet-derived growth factor (PDGF) plays an active role in diabetic kidney disease. Inhibiting PDGF receptor signaling with imatinib significantly reduced kidney damage and disease progression in a mouse model.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic kidney disease is characterized by increased growth factors like PDGF.
- Previous studies did not clarify if PDGF upregulation is a cause or effect in diabetic nephropathy.
Purpose of the Study:
- To investigate PDGF-dependent pathways in diabetic nephropathy development.
- To evaluate the impact of PDGF receptor antagonism on diabetic kidney disease.
Main Methods:
- Utilized a diabetic apolipoprotein E-knockout (apoE-KO) mouse model.
- Induced diabetes with streptozotocin and treated with imatinib (PDGF inhibitor) or placebo.
- Assessed renal function, structure, and molecular markers over 20 weeks.
Main Results:
- Diabetic mice showed increased renal PDGF-B, cell proliferation, alpha-smooth muscle actin, collagen deposition, and macrophage infiltration.
- Imatinib treatment improved renal function and structure, reducing these pathological markers.
- PDGF receptor antagonism ameliorated key molecular and cellular processes in experimental diabetic nephropathy.
Conclusions:
- PDGF signaling is actively involved in the pathophysiology of diabetic nephropathy.
- PDGF receptor antagonism with imatinib shows therapeutic potential for diabetic kidney disease.