title: Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity.
abstract: Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of N(ε)-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of N(ε)-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID.
authors.affiliation: Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Katsuomi
authors.initials: K
authors.lastname: Matsui
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamijo-Ikemorif
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Takashi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D034341:Aristolochic Acids; D001835:Body Weight; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; D018932:Chemokine CCL2; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011347:Procollagen; D016212:Transforming Growth Factor beta; D051398:Aquaporin 1; C000228:aristolochic acid I