Ectopic Expression of Fatty Acid-Binding Protein 4 in the Glomerulus Is Associated with Proteinuria and Renal Dysfunction

被引:45
作者
Tanaka, Marenao [1 ]
Furuhashi, Masato [1 ]
Okazaki, Yusuke [1 ]
Mita, Tomohiro [1 ]
Fuseya, Takahiro [1 ]
Ohno, Kohei [1 ]
Ishimura, Shutaro [1 ]
Yoshida, Hideaki [1 ]
Miura, Tetsuji [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Cardiovasc Renal & Metab Med, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
来源
NEPHRON CLINICAL PRACTICE | 2014年 / 128卷 / 3-4期
关键词
Glomerular endothelial cells; Proteinuria; Renal dysfunction; LIVER-TYPE; APOLIPOPROTEIN-E; KIDNEY; DETERIORATION; DEFICIENT; PODOCYTE; DISEASE; HEART; MICE; AP2;
D O I
10.1159/000368412
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background/Aims: Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones. Among FABPs, FABP1 (liver FABP) is expressed in proximal tubular epithelial cells in the kidney, and urinary FABP1 has been reported to reflect damage of proximal tubular epithelial cells. However, roles of other FABP isoforms in renal pathologies have not been reported. Recently, FABP4 (adipocyte FABP/aP2) was reported to be expressed in peritubular capillaries (PTCs), but not in glomerular capillaries in the normal kidney. We examined the hypothesis that pathological conditions alter the level and localization of FABP4 expression in the kidney, which mediates renal dysfunction. Methods: A total of 112 consecutive patients who underwent renal biopsy were retrospectively enrolled. Expression of FABP4 protein and mRNA in the kidney was examined by immunohistochemistry and in situ hybridization, respectively. The ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area), urinary protein level (U-Protein), and change in estimated glomerular filtration rate (eGFR) 1 year after biopsy were examined. Results: FABP4 protein and mRNA were expressed not only in PTCs, but also in endothelial cells and macrophages in the glomerulus. G-FABP4-Area was correlated with U-Protein (r = 0.497, p < 0.001). As a subanalysis, in patients with IgA nephropathy (n = 34), G-FABP4-Area was significantly larger in cases with an endocapillary proliferative lesion, and change in eGFR was negatively correlated with G-FABP4-Area at baseline (r = -0.537, p = 0.008). Conclusion: Ectopic FABP4 expression in the glomerulus is induced by renal diseases and is closely associated with proteinuria and renal dysfunction. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:345 / 351
页数:7
相关论文
共 25 条
[1]   Predictive Effects of Urinary Liver-Type Fatty Acid-Binding Protein for Deteriorating Renal Function and Incidence of Cardiovascular Disease in Type 2 Diabetic Patients Without Advanced Nephropathy [J].
Araki, Shin-ichi ;
Haneda, Masakazu ;
Koya, Daisuke ;
Sugaya, Takeshi ;
Isshiki, Keiji ;
Kume, Shinji ;
Kashiwagi, Atsunori ;
Uzu, Takashi ;
Maegawa, Hiroshi .
DIABETES CARE, 2013, 36 (05) :1248-1253
[2]   The role of the podocyte in albumin filtration [J].
Brinkkoetter, Paul Thomas ;
Ising, Christina ;
Benzing, Thomas .
NATURE REVIEWS NEPHROLOGY, 2013, 9 (06) :328-336
[3]  
Deen WM, 2001, AM J PHYSIOL-RENAL, V281, pF579
[4]   Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells [J].
Elmasri, Harun ;
Karaaslan, Cagatay ;
Teper, Yaroslav ;
Ghelfi, Elisa ;
Weng, MeiQian ;
Ince, Tan A. ;
Kozakewich, Harry ;
Bischoff, Joyce ;
Cataltepe, Sule .
FASEB JOURNAL, 2009, 23 (11) :3865-3873
[5]   Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets [J].
Furuhashi, Masato ;
Hotamisligil, Goekhan S. .
NATURE REVIEWS DRUG DISCOVERY, 2008, 7 (06) :489-503
[6]   Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice [J].
Furuhashi, Masato ;
Fucho, Raquel ;
Gorgun, Cem Z. ;
Tuncman, Guerol ;
Cao, Haiming ;
Hotamisligil, Goekhan S. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2640-2650
[7]   Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2 [J].
Furuhashi, Masato ;
Tuncman, Guerol ;
Goerguen, Cem Z. ;
Makowski, Liza ;
Atsumi, Genichi ;
Vaillancourt, Eric ;
Kono, Keita ;
Babaev, Vladimir R. ;
Fazio, Sergio ;
Linton, MacRae F. ;
Sulsky, Richard ;
Robl, Jeffrey A. ;
Parker, Rex A. ;
Hotamisligil, Goekhan S. .
NATURE, 2007, 447 (7147) :959-U2
[8]   Lipid Chaperones and Metabolic Inflammation [J].
Furuhashi, Masato ;
Ishimura, Shutaro ;
Ota, Hideki ;
Miura, Tetsuji .
INTERNATIONAL JOURNAL OF INFLAMMATION, 2011, 2011
[9]   Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein [J].
Hotamisligil, GS ;
Johnson, RS ;
Distel, RJ ;
Ellis, R ;
Papaioannou, VE ;
Spiegelman, BM .
SCIENCE, 1996, 274 (5291) :1377-1379
[10]   Capillary Endothelial Fatty Acid Binding Proteins 4 and 5 Play a Critical Role in Fatty Acid Uptake in Heart and Skeletal Muscle [J].
Iso, Tatsuya ;
Maeda, Kazuhisa ;
Hanaoka, Hirofumi ;
Suga, Toshihiro ;
Goto, Kosaku ;
Syamsunarno, Mas Rizky A. A. ;
Hishiki, Takako ;
Nagahata, Yoshiko ;
Matsui, Hiroki ;
Arai, Masashi ;
Yamaguchi, Aiko ;
Abumrad, Nada A. ;
Sano, Motoaki ;
Suematsu, Makoto ;
Endo, Keigo ;
Hotamisligil, Goekhan S. ;
Kurabayashi, Masahiko .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2013, 33 (11) :2549-2557