Liver-type fatty acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction.
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.
Kamijo-Ikemori
Atsuko
A
Internal Medicine, Nephrology and Hypertension, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan.
Sugaya
Takeshi
T
Obama
Ayako
A
Hiroi
Junya
J
Miura
Hiroshi
H
Watanabe
Minoru
M
Kumai
Toshio
T
Ohtani-Kaneko
Ritsuko
R
Hirata
Kazuaki
K
Kimura
Kenjiro
K
D000818:Animals; D043422:Carboxypeptidases A / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D024042:Collagen Type I / Q000032:analysis / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014517:Ureteral Obstruction / Q000473:pathology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024042:Collagen Type I; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D016211:Transforming Growth Factor alpha; D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse