Urinary excretion of IGFBP-1 and -3 correlates with disease activity and differentiates focal segmental glomerulosclerosis and minimal change disease
Urinary excretion of IGFBP-1 and -3 correlates with disease activity and differentiates focal segmental glomerulosclerosis and minimal change disease
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DOI：
10.3109/08977190903512594
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发表时间：
2010-03
期刊：
影响因子：
1.8
通讯作者：
K. Worthmann;Imke Peters;P. Kümpers;M. Saleem;J. Becker;P. A. Agustian;J. Achenbach;H. Haller;M. Schiffer
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文献类型：
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作者：
K. Worthmann;Imke Peters;P. Kümpers;M. Saleem;J. Becker;P. A. Agustian;J. Achenbach;H. Haller;M. Schiffer
肾小球微环境受到从血流中过滤并通过肾小球滤过屏障的循环生长因子的影响。在这项研究中，我们想探讨胰岛素样生长因子结合蛋白（IGFBPs）在两种疾病中的作用，涉及足细胞。我们分析了局灶节段性肾小球硬化症（FSGS）或微小病变性肾小球疾病（MCD）患者的肾小球表达和IGFBP-1、IGFBP-2和IGFBP-3的尿排泄。我们发现，活动性FSGS患者分泌大量的podocalyxin阳性细胞以及IGFBP-1和-3。在人足细胞中，我们可以诱导IGFBP-3的mRNA表达以响应TGF-β，并且在人微血管内皮细胞中，我们可以诱导IGFBP-1和IGFBP-3的mRNA表达以响应TGF-β和缓激肽。我们的结论是IGFBPs在足细胞和内皮细胞的局部表达可能有助于肾小球疾病的发病机制，IGFBP-1和-3是FSGS的潜在的非侵入性标志物。
The glomerular microenvironment is influenced by circulating growth factors that are filtered from the blood stream and pass the glomerular filtration barrier. In this study, we wanted to explore the role of IGF-binding proteins (IGFBPs) in two diseases that concern podocytes. We analyzed glomerular expression and urinary excretion of IGFBP-1, -2, and -3 in patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). We found that patients with active FSGS excrete high amounts of podocalyxin positive cells as well as IGFBP-1 and -3. In human podocytes, we can induce mRNA expression of IGFBP-3 in response to TGF-β and in human microvascular endothelial cells expression of IGFBP-1 and -3 in response to TGF-β and Bradykinin. We conclude that the local expression of IGFBPs in podocytes and endothelial cells might contribute to the pathogenesis of glomerular disease and that IGFBP-1 and -3 are potential non-invasive markers of FSGS.