Glomerular expression and urinary excretion of fatty acid-binding protein 4 in IgA nephropathy
Glomerular expression and urinary excretion of fatty acid-binding protein 4 in IgA nephropathy
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DOI：
10.1007/s40620-022-01551-2
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发表时间：
2023-01-09
影响因子：
3.4
通讯作者：
Furuhashi，Masato
中科院分区：
文献类型：
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作者：
Tanaka，Marenao;Moniwa，Norihito;Furuhashi，Masato
脂肪酸结合蛋白4 （FABP4）由脂肪组织中的脂肪细胞和巨噬细胞分泌，是一种脂肪因子。最近有报道称，除了肝型FABP （L-FABP/FABP1）外，FABP4也在受损的肾小球内皮细胞和肾小球浸润性巨噬细胞中表达，尿型FABP4 （U-FABP4）与肾病患者蛋白尿和肾功能损害有关。然而，肾小球FABP4和U-FABP4之间的联系在IgA肾病（IgAN）中尚未得到充分解决。方法研究FABP4在人和小鼠IgAN中的作用。结果23例IgAN患者肾小球内fabp4阳性面积与肾小球内总面积之比（G-FABP4-Area）和U-FABP4与蛋白尿呈正相关，与eGFR呈负相关。在4 ~ 28周龄雄性组小鼠自发性igan倾向模型中，肾小球内皮细胞和巨噬细胞中检测到FABP4， G-FABP4-Area与尿白蛋白/肌酐比值呈正相关（r= 0.957，P< 0.001）。在人和小鼠IgAN的肾小球中检测内质网应激标志物。在人肾小球内皮细胞中，血管内皮生长因子诱导FABP4从细胞中分泌。用棕榈酸结合的重组FABP4处理人肾小球内皮细胞或小鼠足细胞可显著增加炎症细胞因子和内质网应激标志物的基因表达，并且在抗FABP4抗体存在的情况下，FABP4在足细胞中的作用减弱。结论IgAN患者肾小球中fabp4的表达与蛋白尿有关，U-FABP4水平可作为IgAN患者肾小球损伤的替代生物标志物。
BackgroundFatty acid-binding protein 4 (FABP4) is secreted from adipocytes and macrophages in adipose tissue and acts as an adipokine. It has recently been reported that FABP4, but not liver-type FABP (L-FABP/FABP1), is also expressed in injured glomerular endothelial cells and infiltrating macrophages in the glomerulus and that urinary FABP4 (U-FABP4) is associated with proteinuria and kidney function impairment in nephrotic patients. However, the link between glomerular FABP4 and U-FABP4 has not been fully addressed in IgA nephropathy (IgAN).MethodsWe investigated the involvement of FABP4 in human and mouse IgAN.ResultsIn patients with IgAN (n= 23), the ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area) and U-FABP4 were positively correlated with proteinuria and were negatively correlated with eGFR. In 4–28-week-old male grouped ddY mice, a spontaneous IgAN-prone mouse model, FABP4 was detected in glomerular endothelial cells and macrophages, and G-FABP4-Area was positively correlated with urinary albumin-to-creatinine ratio (r= 0.957,P< 0.001). Endoplasmic reticulum stress markers were detected in glomeruli of human and mouse IgAN. In human renal glomerular endothelial cells, FABP4 was induced by treatment with vascular endothelial growth factor and was secreted from the cells. Treatment of human renal glomerular endothelial cells or mouse podocytes with palmitate-bound recombinant FABP4 significantly increased gene expression of inflammatory cytokines and endoplasmic reticulum stress markers, and the effects of FABP4 in podocytes were attenuated in the presence of an anti-FABP4 antibody.ConclusionFABP4 in the glomerulus contributes to proteinuria in IgAN, and U-FABP4 level is a useful surrogate biomarker for glomerular damage in IgAN.