Podocyte sphingomyelin phosphodiesterase acid-like 3b decreases among children with idiopathic nephrotic syndrome
Podocyte sphingomyelin phosphodiesterase acid-like 3b decreases among children with idiopathic nephrotic syndrome
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DOI：
10.1007/s10157-020-01970-0
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发表时间：
2020-09
影响因子：
2.3
通讯作者：
Shojiro Watanabe;Koji Hirono;Tomomi Aizawa;K. Tsugawa;K. Joh;T. Imaizumi;Hiroshi Tanaka
中科院分区：
文献类型：
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作者：
Shojiro Watanabe;Koji Hirono;Tomomi Aizawa;K. Tsugawa;K. Joh;T. Imaizumi;Hiroshi Tanaka
目的鞘磷脂磷酸二酯酶酸性样3b（SMPDL-3b）是一种细胞骨架的调节剂，在足细胞上表达。最近的报告提出的证据表明，它是直接靶向利妥昔单抗在治疗难治性肾病综合征。然而，SMPDL-3b治疗儿童发病的特发性肾病综合征（INS）的意义尚不清楚。本研究旨在探讨SMPDL-3b在INS患者尿液、血清和活检标本中的表达水平，并探讨其在INS治疗中的意义。方法采用斑点杂交法检测31例INS患者（20例缓解，11例复发）尿液中SMPDL-3b的表达水平。为精确定量分析提供参考，我们采用液相色谱-串联质谱法（LC-MS/MS）检测了10例INS患者缓解期和复发期尿液中SMPDL-3b的排泄量。采用酶联免疫吸附法检测20例INS患者（13例缓解，7例复发或发作）血清SMPDL-3b水平。结果与缓解期和其他类型的蛋白尿伊加肾小球疾病或对照组相比，复发期INS患者的SMPDL-3b尿排泄量显着减少。斑点印迹法和LC-MS/MS法均显示，与缓解期和其他类型的蛋白尿性肾小球疾病或对照组相比，复发期INS患者的SMPDL-3b尿排泄量显着减少。INS缓解组与复发组血清SMPDL-3b水平无明显差异。结论儿童期INS足细胞SMPDL-3b表达明显降低，其尿排泄水平反映了儿童期INS足细胞SMPDL-3b表达的降低。
AimSphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b), a regulator of the cytoskeleton, is expressed on podocytes. Recent reports present evidence that it is directly targeted by rituximab in the treatment of intractable nephrotic syndrome. However, the implications of SMPDL-3b for treatment of paediatric-onset idiopathic nephrotic syndrome (INS) remain unclear. This study aimed to investigate the level of expression of SMPDL-3b in urine, serum, and biopsy specimens and explore its implications in treatment of patients with INS.MethodsLevels of urinary SMPDL-3b among 31 patients (20 in remission and 11 in relapse) with INS were analysed by dot blotting. For reference of precise quantitative analysis, we examined urinary excretion of SMPDL-3b from 10 patients with INS by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in both remitted and relapsed status. The levels of serum SMPDL-3b among 20 patients (13 in remission and 7 in relapse or onset) with INS were also measured using enzyme-linked immunosorbent assay. Further, the immunoreactivity of SMPDL-3b in the biopsy specimens obtained from patients with INS was compared with those from patients with proteinuric IgA nephropathy, lupus nephritis, and non-proteinuric controls.ResultsUrinary excretion of SMPDL-3b in patients with INS was significantly decreased in relapse cases compared with cases of remission and other types of proteinuric glomerular disease or controls by both dot blotting and LC–MS/MS method. On the other hand, serum SMPDL-3b level in INS was not different between cases of remission and relapse. Glomerular immunoreactivity of SMPDL-3b in patient with INS in remission was almost the same level to that of control.ConclusionThe expression of SMPDL-3b on podocytes is specifically decreased in paediatric-onset INS and its urinary excretion level reflects such conditions.