Ectopic Expression of Fatty Acid-Binding Protein 4 in the Glomerulus Is Associated with Proteinuria and Renal Dysfunction
Ectopic Expression of Fatty Acid-Binding Protein 4 in the Glomerulus Is Associated with Proteinuria and Renal Dysfunction
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DOI：
10.1159/000368412
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Miura, Tetsuji
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文献类型：
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作者：
Tanaka, Marenao;Furuhashi, Masato;Miura, Tetsuji
背景/目的：脂肪酸结合蛋白（Fatty acid-binding proteins，FABPs）是一类细胞内的脂质伴侣蛋白。在FABP中，FABP 1（肝FABP）在肾脏的近端肾小管上皮细胞中表达，并且据报道尿FABP 1反映近端肾小管上皮细胞的损伤。然而，其他FABP亚型在肾脏病理中的作用尚未报道。最近，FABP 4（脂肪细胞FABP/aP 2）被报道在正常肾脏的管周毛细血管（PTC）中表达，而在肾小球毛细血管中不表达。我们研究了病理条件改变肾脏中FABP 4表达水平和定位的假设，FABP 4介导肾功能障碍。方法：回顾性纳入112例连续行肾活检的患者。采用免疫组化和原位杂交方法检测肾脏FABP 4蛋白和mRNA的表达。检测FABP 4阳性面积与肾小球总面积的比值（G-FABP 4-Area）、尿蛋白水平（U-Protein）和活检后1年估计肾小球滤过率（eGFR）的变化。结果：FABP 4蛋白和mRNA不仅在PTC中表达，而且在肾小球内皮细胞和巨噬细胞中也有表达。G-FABP 4-面积与U-蛋白相关（r = 0.497，p < 0.001）。作为亚组分析，在伊加肾病患者（n = 34）中，毛细血管内增生性病变患者的G-FABP 4-面积显著更大，基线时eGFR的变化与G-FABP 4-面积呈负相关（r =-0.537，p = 0.008）。结论：FABP 4在肾小球的异位表达是由肾脏疾病引起的，并与蛋白尿和肾功能不全密切相关。(C)2015 S. Karger AG，巴塞尔
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