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大鼠肾脏中的金属蛋白酶meprin β:肾小球定位及在肾小球肾炎中的差异表达

Metalloprotease meprin beta in rat kidney: glomerular localization and differential expression in glomerulonephritis.

作者信息

Oneda Beatrice, Lods Nadège, Lottaz Daniel, Becker-Pauly Christoph, Stöcker Walter, Pippin Jeffrey, Huguenin Maya, Ambort Daniel, Marti Hans-Peter, Sterchi Erwin E

机构信息

Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.

出版信息

PLoS One. 2008 May 28;3(5):e2278. doi: 10.1371/journal.pone.0002278.

Abstract

Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase found in microvillar membranes of kidney proximal tubular epithelial cells. Here, we present the first report on the expression of meprin beta in rat glomerular epithelial cells and suggest a potential involvement in experimental glomerular disease. We detected meprin beta in glomeruli of immunostained rat kidney sections on the protein level and by quantitative RT-PCR of laser-capture microdissected glomeruli on the mRNA level. Using immuno-gold staining we identified the membrane of podocyte foot processes as the main site of meprin beta expression. The glomerular meprin beta expression pattern was altered in anti-Thy 1.1 and passive Heymann nephritis (PHN). In addition, the meprin beta staining pattern in the latter was reminiscent of immunostaining with the sheep anti-Fx1A antiserum, commonly used in PHN induction. Using Western blot and immunoprecipitation assays we demonstrated that meprin beta is recognized by Fx1A antiserum and may therefore represent an auto-antigen in PHN. In anti-Thy 1.1 glomerulonephritis we observed a striking redistribution of meprin beta in tubular epithelial cells from the apical to the basolateral side and the cytosol. This might point to an involvement of meprin beta in this form of glomerulonephritis.

摘要

膜金属蛋白酶(EC 3.4.24.18)是一种寡聚金属内肽酶,存在于肾近端小管上皮细胞的微绒毛膜中。在此,我们首次报道了膜金属蛋白酶β在大鼠肾小球上皮细胞中的表达,并提示其可能参与实验性肾小球疾病。我们通过免疫染色在大鼠肾切片的肾小球中检测到了膜金属蛋白酶β的蛋白水平,并通过对激光捕获显微切割的肾小球进行定量逆转录聚合酶链反应检测到了其mRNA水平。使用免疫金染色,我们确定足细胞足突膜是膜金属蛋白酶β表达的主要部位。在抗Thy 1.1和被动型Heymann肾炎(PHN)中,肾小球膜金属蛋白酶β的表达模式发生了改变。此外,后者的膜金属蛋白酶β染色模式让人联想到常用于诱导PHN的羊抗Fx1A抗血清的免疫染色。使用蛋白质印迹和免疫沉淀分析,我们证明膜金属蛋白酶β可被Fx1A抗血清识别,因此可能是PHN中的一种自身抗原。在抗Thy 1.1肾小球肾炎中,我们观察到膜金属蛋白酶β在肾小管上皮细胞中从顶端向基底外侧和细胞质发生了显著的重新分布。这可能表明膜金属蛋白酶β参与了这种形式的肾小球肾炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6cd/2386549/e8589283ea85/pone.0002278.g001.jpg

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