Decreased renal corin expression contributes to sodium retention in proteinuric kidney diseases.
Decreased renal corin expression contributes to sodium retention in proteinuric kidney diseases.
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DOI：
10.1038/ki.2010.197
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发表时间：
2010-10
影响因子：
19.6
通讯作者：
Theilig, Franziska
中科院分区：
文献类型：
--
作者：
Polzin, Danny;Kaminski, Henriette J.;Kastner, Christian;Wang, Wei;Kraemer, Stephanie;Gambaryan, Stepan;Russwurm, Michael;Peters, Harm;Wu, Qingyu;Vandewalle, Alain;Bachmann, Sebastian;Theilig, Franziska
患有蛋白尿性肾病的患者经常会出现盐和水潴留的症状。据推测，Na + 吸收失调是由于上皮钠通道 (ENaC) 的蛋白水解裂解增加和 Na,K-ATP 酶表达增加所致。微阵列分析发现，嘌呤霉素氨基核苷诱导的肾病综合征 (PAN) 和急性抗 Thy1 肾小球肾炎 (GN) 大鼠模型的肾脏中 corin mRNA 表达降低。 Corin 已被证明可将前心房钠尿肽 (ANP) 转化为 ANP。由于 ANP 抵抗被认为是导致容量滞留的一种机制，因此进行了实验来分析 corin 的肾脏表达和功能。免疫组织化学显示 corin 与 ANP 共定位。在 PAN 和 GN 中，肾脏表现出伴随的 pro-ANP 增加和 ANP 蛋白表达水平降低，这与低 corin 水平一致。重要的是，与野生型小鼠相比，corin -/− 小鼠的肾脏显示肾 β-ENaC、磷酸二酯酶 5 (PDE5) 和蛋白激酶 G II (PKGII) 水平升高。在细胞培养实验中观察到类似的表达谱，表明 PDE5 和 PKGII 的增加可以解释 PAN 和 GN 中观察到的 β-ENaC 的增加。总之，我们的数据为肾脏疾病容量潴留机制提供了新的见解，corin 作为一种重要的新介质，通过 PKGII 诱导和 ENaC 激活发挥作用。
Patients with proteinuric kidney diseases often experience symptoms of salt and water retention. It has been hypothesized that the dysregulated Na+ absorption is due to increased proteolytic cleavage of epithelial sodium channel (ENaC) and increased Na,K-ATPase expression. Microarray analysis identified a reduced corin mRNA expression in kidneys from rat models of puromycin aminonucleoside-induced nephrotic syndrome (PAN) and acute anti-Thy1 glomerulonephritis (GN). Corin has been shown to convert pro-atrial natriuretic peptide (ANP) to ANP. Because ANP resistance has been assumed to be a mechanism accounting for volume retention, experiments were undertaken to analyze the renal expression and function of corin. Immunohistochemistry revealed that corin co-localized with ANP. In PAN and GN, kidneys exhibited concomitant increased pro-ANP and decreased ANP protein expression levels consistent with low corin levels. Importantly, kidneys from corin −/− mice showed increased levels of renal β-ENaC, phosphodiesterase 5 (PDE5) and protein kinase G II (PKGII) when compared to wild-type mice. Similar expression profile was observed in cell culture experiments suggesting that the increase in PDE5 and PKGII could account for the increase in β-ENaC as observed in PAN and GN. To conclude, our data provide novel insights into the mechanisms of volume retention in renal disease with corin as an important new mediator that acts through PKGII induction and ENaC activation.
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DOI：
10.1073/pnas.0407234102
发表时间：
2005-01-18
影响因子：
11.1
作者：
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发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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