Increased expression of secreted frizzled-related protein 4 in polycystic kidneys.
Increased expression of secreted frizzled-related protein 4 in polycystic kidneys.
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DOI：
10.1681/asn.2008040345
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Daniel Romaker;Michael Puetz;S. Teschner;J. Donauer;M. Geyer;P. Gerke;B. Rumberger;B. Dworniczak;P. Pennekamp;B. Buchholz;H. Neumann;R. Kumar;J. Gloy;K. Eckardt;G. Walz
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文献类型：
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作者：
Daniel Romaker;Michael Puetz;S. Teschner;J. Donauer;M. Geyer;P. Gerke;B. Rumberger;B. Dworniczak;P. Pennekamp;B. Buchholz;H. Neumann;R. Kumar;J. Gloy;K. Eckardt;G. Walz
常染色体显性多囊肾病是一种常见的伴有进行性肾功能衰竭的遗传性疾病。虽然囊肿生长和周围组织的压迫可能导致一些肾组织损失，但导致ADPKD患者进行性肾衰竭的其他因素尚未完全了解。在这里，我们报告分泌型卷曲相关蛋白4（sFRP4）在人类ADPKD和四种不同的PKD动物模型中上调，表明sFRP4表达是由囊肿形成的共同机制触发的。来自ADPKD肾脏的囊液激活sFRP4启动子并诱导肾小管上皮细胞系中sFRP4蛋白的产生。血管加压素2受体的拮抗作用阻断了启动子活性和肾小管sFRP4表达。此外，sFRP4选择性地影响经典Wnt信号级联的成员，并促进斑马鱼原肾的囊形成。在PKD患者和动物的尿液中均检测到sFRP4，提示sFRP4可能是监测ADPKD进展的潜在生物标志物。总之，这些观察结果表明SFRP 4在ADPKD的发病机制中具有潜在作用。
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease associated with progressive renal failure. Although cyst growth and compression of surrounding tissue may account for some loss of renal tissue, the other factors contributing to the progressive renal failure in patients with ADPKD are incompletely understood. Here, we report that secreted frizzled-related protein 4 (sFRP4) is upregulated in human ADPKD and in four different animal models of PKD, suggesting that sFRP4 expression is triggered by a common mechanism that underlies cyst formation. Cyst fluid from ADPKD kidneys activated the sFRP4 promoter and induced production of sFRP4 protein in renal tubular epithelial cell lines. Antagonism of the vasopressin 2 receptor blocked both promoter activity and tubular sFRP4 expression. In addition, sFRP4 selectively influenced members of the canonical Wnt signaling cascade and promoted cystogenesis of the zebrafish pronephros. sFRP4 was detected in the urine of both patients and animals with PKD, suggesting that sFRP4 may be a potential biomarker for monitoring the progression of ADPKD. Taken together, these observations suggest a potential role for SFRP4 in the pathogenesis of ADPKD.