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(American Journal of Pathology. 2006;169:1107-1117.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060131

Liver-Type Fatty Acid-Binding Protein Attenuates Renal Injury Induced by Unilateral Ureteral Obstruction

Atsuko Kamijo-Ikemori^*, Takeshi Sugaya^*, Ayako Obama^*, Junya Hiroi, Hiroshi Miura^*, Minoru Watanabe, Toshio Kumai, Ritsuko Ohtani-Kaneko, Kazuaki Hirata and Kenjiro Kimura^*

From Internal Medicine, Division of Nephrology and Hypertension,^* and the Departments of Anatomy and Pharmacology, St. Marianna University School of Medicine, Kawasaki; and CMIC Company, Limited, Tokyo, Japan

Liver-type fatty-acid-binding protein (L-FABP), which has high affinity for long-chain fatty acid oxidation products, may be an effective endogenous antioxidant. To examine the role of L-FABP in tubulointerstitial damage, we used a unilateral ureteral obstruction (UUO) model. We established human L-FABP (hL-FABP) gene transgenic (Tg) mice and compared the tubulointerstitial pathology of the Tg mice (n = 23) with that of the wild-type (WT) mice (n = 23). Mice were sacrificed on days 2, 4, 5, or 7 after UUO. Although mouse L-FABP was not expressed in WT mice, hL-FABP was expressed in the proximal tubules of the Tg mice with UUO (UUO-Tg) and in sham-operated Tg mice. The expression of renal hL-FABP was significantly increased in UUO-Tg compared with sham-operated Tg mice. The number of macrophages (F4/80) infiltrating the interstitium and the level of expression of MCP-1 and MCP-3 were significantly lower in UUO-Tg kidneys compared with UUO-WT kidneys. In UUO-Tg kidneys, the degree of the tubulointerstitial injury and the deposition of type I collagen were significantly lower than that of UUO-WT kidneys. On day 7, lipid peroxidation product accumulated in the UUO-WT kidneys but not in that of UUO-Tg kidneys. In conclusion, renal L-FABP may reduce the oxidative stress in the UUO model, ameliorating tubulointerstitial damage.

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