title: Human liver-type fatty acid-binding protein protects against tubulointerstitial injury in aldosterone-induced renal injury.
abstract: To demonstrate the renoprotective function of human liver-type fatty acid-binding protein (hL-FABP) expressed in proximal tubules in aldosterone (Aldo)-induced renal injury, hL-FABP chromosomal transgenic (Tg) and wild-type (WT) mice received systemic Aldo infusions (Tg-Aldo and WT-Aldo, respectively) were given 1% NaCl water for 28 days. In this model, elevation of systolic blood pressure, monocyte chemoattractant protein-1 expression, macrophage infiltration in the interstitium, tubulointerstitial damage, and depositions of type I and III collagens were observed. Elevation of systolic blood pressure did not differ in WT-Aldo vs. Tg-Aldo animals, however, renal injury was suppressed in Tg-Aldo compared with WT-Aldo mice. Dihydroethidium fluorescence was used to evaluate reactive oxidative stress, which was suppressed in Tg-Aldo compared with WT-Aldo mice. Gene expression of angiotensinogen in the kidney was upregulated, and excretion of urinary angiotensinogen was increased in WT-Aldo mice. This exacerbation was suppressed in Tg-Aldo mice. Expression of hL-FABP was upregulated in proximal tubules of Tg-Aldo mice. Urinary excretion of hL-FABP was significantly greater in Tg-Aldo than in Tg-control mice. In conclusion, hL-FABP ameliorated the tubulointerstitial damage in Aldo-induced renal injury via reducing oxidative stress and suppressing activation of the intrarenal renin-angiotensin system.
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan a2kamijo@marianna-u.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamijo-Ikemori
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shibagaki
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Hoshino
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and.
authors.forename: Kimie
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Igarashi-Migitaka
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; and.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000378:metabolism*; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D051437:Renal Insufficiency / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012084:Renin-Angiotensin System
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024042:Collagen Type I; D024061:Collagen Type III; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D000808:Angiotensinogen; D000450:Aldosterone
keywords: L-FABP; activation of the intrarenal renin-angiotensin system; aldosterone; oxidative stress; tubulointerstitial damage