NDT Advance Access published online on October 14, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn573
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Amelioration of diabetic tubulointerstitial damage in liver-type fatty acid binding protein transgenic mice
1 Division of Nephrology and Hypertension, Internal Medicine 2 Department of Anatomy, St Marianna University School of Medicine, Kawasaki 3 CMIC CO. Ltd, Tokyo, Japan
Correspondence and offprint requests to: Kenjiro Kimura, Division of Medicine, Nephrology and Hypertension, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan. Tel: +81-44-977-8111; Fax: +81-44-977-7873; E-mail: kimura{at}marianna-u.ac.jp
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Abstract |
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Background. Renoprotection of liver-type fatty acid binding protein (L-FABP) was demonstrated in a streptozotocin (STZ)-induced diabetic mouse model.
Methods. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were divided into two groups: diabetic mice were uninephrectomized and injected with STZ; control mice were uninephrectomized and injected with a citrate buffer alone. Although mouse L-FABP was not expressed in WT mice, hL-FABP was expressed in the proximal tubules of the diabetic Tg mice and in the control Tg mice at 8 and 14 weeks after these injections.
Results. The expression of renal hL-FABP increased significantly in diabetic Tg mice compared to control Tg mice. A number of macrophages (F4/80) infiltrating the interstitium, the gene expressions of MCP-1, MCP-3, TGF-β, Fas, Bax and RAGE were significantly lower in diabetic Tg kidneys compared with diabetic WT kidneys. In the diabetic Tg kidneys, the degree of the tubulointerstitial injury and the deposition of type IV collagen were significantly lower than that of diabetic WT kidneys. The expressions of catalase and glutathione peroxidase-1 were significantly lower in diabetic Tg kidneys compared with diabetic WT kidneys.
Conclusions. Renal L-FABP ameliorated the tubulointerstitial damage of type 1 diabetic mice.
Keywords: diabetic nephropathy; liver-type fatty acid binding protein; proximal tubule; tubulointerstitial damage
Received for publication: 21. 6.08
Accepted in revised form: 18. 9.08
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