Estrogen negatively regulates the renal epithelial sodium channel (ENaC) by promoting Derlin-1 expression and AMPK activation
Estrogen negatively regulates the renal epithelial sodium channel (ENaC) by promoting Derlin-1 expression and AMPK activation
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雌激素通过促进 Derlin-1 表达和 AMPK 激活负向调节肾上皮钠通道 (ENaC)
DOI：
10.1038/s12276-019-0253-z
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发表时间：
2019-05
影响因子：
12.8
通讯作者：
Liang Xiubin
中科院分区：
文献类型：
--
作者：
Zhang Xue;Ge Yamei;Bukhari Ashfaq Ahmad Shah;Zhu Qian;Shen Yachen;Li Min;Sun Hui;Su Dongming;Liang Xiubin
肾远端肾单位上皮钠通道（ENaC）的主要功能是调节水钠平衡和稳定血压。雌激素对钠和水平衡以及绝经前血压有重要影响，但其在ENaC功能调节中的作用尚未完全了解。雌性Sprague-Dawley大鼠在双侧卵巢切除术后用17β-雌二醇处理6周。分析血浆雌激素、醛固酮、肌酐和电解质，并通过免疫组织化学和蛋白质印迹法测定肾脏中α-ENaC和derlin-1蛋白的表达。用Western blotting和real-time PCR检测雌激素处理后小鼠肾集合管上皮细胞（mpkCCDc 14）中α-ENaC、derlin-1、AMPK及相关分子的表达水平。采用免疫荧光和免疫共沉淀技术检测α-ENaC与derlin-1的结合和α-ENaC的泛素化。结果表明，雌激素的损失升高收缩压在卵巢切除（OVX）大鼠。OVX大鼠肾脏α-ENaC表达增加，derlin-1表达减少。相反，雌激素处理降低了mpkCCDc 14细胞中α-ENaC的表达，但增加了derlin-1的表达。此外，雌激素通过促进α-ENaC与derlin-1的相互作用诱导α-ENaC泛素化，并诱导AMPK磷酸化。我们的研究表明，雌激素通过上调derlin-1和激活AMPK降低去卵巢大鼠ENaC表达和血压。
The main functions of the epithelial sodium channel (ENaC) in the kidney distal nephron are mediation of sodium and water balance and stabilization of blood pressure. Estrogen has important effects on sodium and water balance and on premenopausal blood pressure, but its role in the regulation of ENaC function is not fully understood. Female Sprague–Dawley rats were treated with 17β-estradiol for 6 weeks following bilateral ovariectomy. Plasma estrogen, aldosterone, creatinine, and electrolytes were analyzed, and α-ENaC and derlin-1 protein expression in the kidney was determined by immunohistochemistry and western blotting. The expression levels of α-ENaC, derlin-1, AMPK, and related molecules were also examined by western blotting and real-time PCR in cultured mouse renal collecting duct (mpkCCDc14) epithelial cells following estrogen treatment. Immunofluorescence and coimmunoprecipitation were performed to detect α-ENaC binding with derlin-1 and α-ENaC ubiquitination. The results demonstrated that the loss of estrogen elevated systolic blood pressure in ovariectomized (OVX) rats. OVX rat kidneys showed increased α-ENaC expression but decreased derlin-1 expression. In contrast, estrogen treatment decreased α-ENaC expression but increased derlin-1 expression in mpkCCDc14 cells. Moreover, estrogen induced α-ENaC ubiquitination by promoting the interaction of α-ENaC with derlin-1 and evoked phosphorylation of AMPK in mpkCCDc14 cells. Our study indicates that estrogen reduces ENaC expression and blood pressure in OVX rats through derlin-1 upregulation and AMPK activation.
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DOI：
10.1085/jgp.200409124
发表时间：
2005-01
期刊：
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影响因子：
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影响因子：
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作者：
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作者：
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