Deakin University
Browse
smith-imatinibattentuates-2005.pdf (1.01 MB)

Imatinib attenuates diabetic nephropathy in apolipoprotein E-knockout mice

Download (1.01 MB)
journal contribution
posted on 2005-02-01, 00:00 authored by M Lassila, K Jandeleit-Dahm, K K Seah, Craig SmithCraig Smith, A C Calkin, T J Allen, M E Cooper
In the diabetic kidney, clinical as well as experimental observations have shown an upregulation of growth factors such as PDGF. These studies, however, were not designed to address whether upregulation of PDGF is merely a manifestation of diabetic renal injury or whether PDGF plays an active role in the pathophysiology of diabetic nephropathy. The objectives of this study were first to assess whether PDGF-dependent pathways are involved in the development of diabetic nephropathy and second to determine the effects of PDGF receptor antagonism on this disorder and associated molecular and cellular processes. This study used the diabetic apolipoprotein E-knockout (apoE-KO) mouse, a recently described model of accelerated diabetic nephropathy. Diabetes was induced by injection of streptozotocin in 6-wk-old apoE-KO mice. Diabetic animals received treatment with a tyrosine kinase inhibitor that inhibits PDGF action, imatinib (STI-571, 10 mg/kg per d orally) or no treatment for 20 wk. Nondiabetic apoE-KO mice served as controls. This model of accelerated renal disease with albuminuria as well as glomerular and tubulointerstitial injury was associated with increased renal expression of PDGF-B, proliferating cells, and α-smooth muscle actin-positive cells. Furthermore, there was increased accumulation of type I and type IV collagen as well as macrophage infiltration. Imatinib treatment ameliorated both renal functional and structural parameters of diabetes as well as overexpression of a number of growth factors, collagens, proliferating cells, α-smooth muscle actin-positive cells, and macrophage infiltration within the kidney. Tyrosine kinase inhibition with imatinib seems to retard the development of experimental diabetic nephropathy.

History

Journal

Journal of the American society of nephrology

Volume

16

Issue

2

Pagination

363 - 373

Publisher

American Society of Nephrology

Location

[Washington, D.C.]

ISSN

1046-6673

eISSN

1533-3450

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, American Society of Nephrology

Usage metrics

    Research Publications

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC