Impaired epithelial Na+ channel activity contributes to cystogenesis and development of autosomal recessive polycystic kidney disease in PCK rats.
Impaired epithelial Na+ channel activity contributes to cystogenesis and development of autosomal recessive polycystic kidney disease in PCK rats.
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DOI：
10.1038/pr.2014.145
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发表时间：
2015-01
影响因子：
3.6
通讯作者：
Staruschenko, Alexander
中科院分区：
文献类型：
--
作者：
Pavlov, Tengis S.;Levchenko, Vladislav;Ilatovskaya, Daria V.;Palygin, Oleg;Staruschenko, Alexander
常染色体隐性遗传性多囊肾病（ARPKD）是一种遗传性疾病，其特征是肾小管上皮细胞起源的肾囊肿的发展。上皮Na+通道（ENaC）负责醛固酮敏感性远端肾单位的钠重吸收。在这里，我们研究了ENaC的表达和活性在囊性组织取自大鼠ARPKD。用在饮用水中给予的选择性ENaC抑制剂苯扎明治疗PCK大鼠，并在4或12周后评估肾脏形态畸形的严重程度。采用免疫组织化学和膜片钳电生理技术检测ENaC和AQP 2的表达及ENaC活性。与溶剂处理动物相比，苯扎明处理加剧了囊肿的发展。相反，12周的袢利尿剂呋塞米治疗对膀胱生成没有影响。单通道膜片钳分析表明，ENaC活性在新鲜分离的囊性上皮细胞显着低于非囊性收集管分离的PCK或正常的Sprague-Dawley大鼠。免疫组织化学分析证实，与PCK大鼠肾脏的非扩张小管相比，囊肿中的β-ENaC和AQP 2表达降低。我们证明，囊性上皮表现出低ENaC活性，这种现象可能有助于囊肿的进展。
Autosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder characterized by the development of renal cysts of the tubular epithelial cell origin. Epithelial Na+ channel (ENaC) is responsible for sodium reabsorption in the aldosterone-sensitive distal nephron. Here we investigated the ENaC expression and activity in cystic tissue taken from rats with ARPKD. PCK rats were treated with the selective ENaC inhibitor benzamil given in the drinking water, and after 4 or 12 weeks the severity of morphological malformations in the kidneys was assessed. ENaC and AQP2 expression and ENaC activity were tested with immunohistochemistry and patch clamp electrophysiology, respectively. Treatment with benzamil exacerbated development of cysts compared to the vehicle-treated animals. In contrast, the 12 weeks treatment with a loop diuretic furosemide had no effect on cystogenesis. Single channel patch clamp analysis revealed that ENaC activity in the freshly isolated cystic epithelium was significantly lower than in the non-cystic collecting ducts isolated from PCK or normal Sprague-Dawley rats. Immunohistochemical analysis confirmed that β-ENaC and AQP2 expressions in cysts are decreased compared to non-dilated tubules from PCK rat kidneys. We demonstrated that cystic epithelium exhibits low ENaC activity and this phenomenon can contribute to cyst progression.
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影响因子：
3.6
作者：
Sweeney, William E., Jr.;Avner, Ellis D.
通讯作者：
Avner, Ellis D.
影响因子：
5.8
作者：
Staruschenko A
通讯作者：
Staruschenko A
影响因子：
3.3
作者：
Ryan S;Verghese S;Cianciola NL;Cotton CU;Carlin CR
通讯作者：
Carlin CR
DOI：
10.1073/pnas.1216830110
发表时间：
2012-12-26
影响因子：
11.1
作者：
Kwon, Michelle;Pavlov, Tengis S.;Park, Frank
通讯作者：
Park, Frank
影响因子：
5.6
作者：
Levchenko, Vladislav;Zheleznova, Nadezhda N.;Staruschenko, Alexander
通讯作者：
Staruschenko, Alexander