Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys.
Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys.
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DOI：
10.1371/journal.pone.0253197
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Bruggeman LA
中科院分区：
文献类型：
--
作者：
Blessing NA;Wu Z;Madhavan SM;Choy JW;Chen M;Shin MK;Hoek M;Sedor JR;O'Toole JF;Bruggeman LA
与APOL1多态性和非糖尿病慢性肾脏病（CKD）风险相关的发病机制尚未完全了解。先前的研究已经最小化了循环APOL1蛋白的因果作用，因此理解肾脏发病机制的努力集中在肾细胞中表达的APOL1。在报道表达APOL 1的肾细胞中，近端小管表达模式在已发表的报道中不一致，APOL 1是否由近端小管合成或血液中的APOL 1蛋白是否被近端小管过滤和重吸收仍不清楚。采用蛋白质和mRNA原位方法，检测了正常人和APOL 1细菌人工染色体转基因小鼠（有和无蛋白尿）肾脏中APOL 1的表达模式。APOL1蛋白和mRNA在足细胞和内皮细胞中表达，在肾小管上皮细胞中未见表达。在蛋白尿的情况下，血浆APOL 1蛋白似乎没有被近端小管过滤或重吸收。对先前研究中使用的商业抗体的并行检查表明，近端小管中APOL 1的原始报告可能反映了抗体的非特异性。因此，足细胞和内皮细胞中的APOL1表达应该仍然是APOL1介导的肾脏疾病机制研究的焦点。
The mechanism of pathogenesis associated with APOL1 polymorphisms and risk for non-diabetic chronic kidney disease (CKD) is not fully understood. Prior studies have minimized a causal role for the circulating APOL1 protein, thus efforts to understand kidney pathogenesis have focused on APOL1 expressed in renal cells. Of the kidney cells reported to express APOL1, the proximal tubule expression patterns are inconsistent in published reports, and whether APOL1 is synthesized by the proximal tubule or possibly APOL1 protein in the blood is filtered and reabsorbed by the proximal tubule remains unclear. Using both protein and mRNA in situ methods, the kidney expression pattern of APOL1 was examined in normal human and APOL1 bacterial artificial chromosome transgenic mice with and without proteinuria. APOL1 protein and mRNA was detected in podocytes and endothelial cells, but not in tubular epithelia. In the setting of proteinuria, plasma APOL1 protein did not appear to be filtered or reabsorbed by the proximal tubule. A side-by-side examination of commercial antibodies used in prior studies suggest the original reports of APOL1 in proximal tubules likely reflects antibody non-specificity. As such, APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies in the APOL1-mediated kidney diseases.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
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Pollak MR
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影响因子：
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作者：
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影响因子：
13.6
作者：
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影响因子：
13.6
作者：
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影响因子：
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作者：
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