Liver-type fatty acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction

被引:83
作者
Kamijo-Ikemori, Atsuko
Sugaya, Takeshi
Obama, Ayako
Hiroi, Junya
Miura, Hiroshi
Watanabe, Minoru
Kumai, Toshio
Ohtani-Kaneko, Ritsuko
Hirata, Kazuaki
Kimura, Kenjiro
机构
[1] St Marianna Univ, Sch Med, Div Nephrol & Hypertens, Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan
[2] St Marianna Univ, Sch Med, Dept Anat, Kawasaki, Kanagawa 2168511, Japan
[3] St Marianna Univ, Sch Med, Dept Pharmacol, Kawasaki, Kanagawa 2168511, Japan
[4] CMIC Co Ltd, Tokyo, Japan
关键词
D O I
10.2353/ajpath.2006.060131
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:1107 / 1117
页数:11
相关论文
共 44 条
[1]  
APPLEGATE LA, 1991, CANCER RES, V51, P974
[2]   Obstructive nephropathy: Insights from genetically engineered animals [J].
Bascands, JL ;
Schanstra, JP .
KIDNEY INTERNATIONAL, 2005, 68 (03) :925-937
[3]   An imbalance in antioxidant defense affects cellular function: the pathophysiological consequences of a reduction in antioxidant defense in the glutathione peroxidase-1 (Gpx1) knockout mouse [J].
de Haan, JB ;
Crack, PJ ;
Flentjar, N ;
Iannello, RC ;
Hertzog, PJ ;
Kola, I .
REDOX REPORT, 2003, 8 (02) :69-79
[4]   Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide [J].
de Haan, JB ;
Bladier, C ;
Griffiths, P ;
Kelner, M ;
O'Shea, RD ;
Cheung, NS ;
Bronson, RT ;
Silvestro, MJ ;
Wild, S ;
Zheng, SS ;
Beart, PM ;
Hertzog, PJ ;
Kola, I .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (35) :22528-22536
[5]   Interstitial fibrosis in hypercholesterolemic rats: Role of oxidation, matrix synthesis, and proteolytic cascades [J].
Eddy, AA ;
Liu, E ;
McCulloch, L .
KIDNEY INTERNATIONAL, 1998, 53 (05) :1182-1189
[6]   Binding of 13-HODE and 15-HETE to phospholipid bilayers, albumin, and intracellular fatty acid binding proteins - Implications for transmembrane and intracellular transport and for protection from lipid peroxidation [J].
Ek-von Mentzer, BA ;
Zhang, FL ;
Hamilton, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (19) :15575-15580
[7]   Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury [J].
Furuichi, K ;
Wada, T ;
Iwata, Y ;
Kitagawa, K ;
Kobayashi, K ;
Hashimoto, H ;
Ishiwata, Y ;
Tomosugi, N ;
Mukaida, N ;
Matsushima, K ;
Egashira, K ;
Yokoyama, H .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2003, 14 (04) :1066-1071
[8]   Liver fatty acid-binding protein targets fatty acids to the nucleus - Real time confocal and multiphoton fluorescence imaging in living cells [J].
Huang, H ;
Starodub, O ;
McIntosh, A ;
Kier, AB ;
Schroeder, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (32) :29139-29151
[9]   Liver fatty acid-binding protein colocalizes with peroxisome proliferator activated receptor α and enhances ligand distribution to nuclei of living cells [J].
Huang, H ;
Starodub, O ;
McIntosh, A ;
Atshaves, BP ;
Woldegiorgis, G ;
Kier, AB ;
Schroeder, F .
BIOCHEMISTRY, 2004, 43 (09) :2484-2500
[10]  
ISSEMANN I, 1990, NATURE, V347, P645, DOI 10.1038/347645a0