Zhen-wu-tang attenuates Adriamycin-induced nephropathy via regulating AQP2 and miR-92b
Zhen-wu-tang attenuates Adriamycin-induced nephropathy via regulating AQP2 and miR-92b
复制标题
真武汤通过调节 AQP2 和 miR-92b 减轻阿霉素诱导的肾病
DOI：
10.1016/j.biopha.2018.10.146
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发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Zhou, Jiu-yao
中科院分区：
文献类型：
--
作者：
Liang, Chun-ling;Zhang, Pei-chun;Zhou, Jiu-yao
肾病综合征（NS）以蛋白尿、低白蛋白血症和水肿为特征。水钠代谢紊乱是NS发生发展的重要机制。真武汤在中国和日本传统上用于治疗水肿病。本研究旨在观察ZWT对阿霉素诱导的NS大鼠的保护作用，并探讨ZWT抗NS的可能机制。结果表明，ZWT能改善肾功能损害，调节肾脏水平衡。重要的是，ZWT增加水通道蛋白-2（AQP 2）的表达，其在维持体内水分稳态中起关键作用。此外，我们确定了NS大鼠中的miRNAs表达模式。通过生物信息学预测和miR-92 b模拟物或抑制剂的体外实验，我们确定miR-92 b可能是AQP 2的调节剂。ZWT可降低miR-92 b的表达，逆转miR-92 b对AQP 2的影响。我们进一步证明了miR-92 b通过靶向AQP 2的3 'UTR直接调控AQP 2的表达。这些结果表明，ZWT可能通过调节AQP 2和miR-92 b来减轻阿霉素肾病的肾水肿。
Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia and edema. The disorder of sodium and water metabolism is a critical mechanism regulating the origination and progression of NS. Zhen-wu-tang (ZWT) has been traditionally used to treat edema disease in China and Japan. The present study was carried out to assess the protective effect of ZWT in Adriamycin-induced (ADR) NS rats and investigate the potential anti-NS mechanisms of ZWT. We found that ZWT treatment ameliorate impaired kidney function and regulate water balance of kidney. Importantly, ZWT increased the expression of Aquaporin-2 (AQP2) which play key roles in maintaining body water homeostasis. Additionally, we determined miRNAs expression patterns in NS rats. Using bioinformatics prediction and miR-92b mimic or inhibitor in vitro, we identified miR-92b as a possible modulator of AQP2. Also we found that ZWT can decrease the expression of miR-92b and reverse the effect of miR92b on AQP2 in vitro. We further demonstrated that miR-92b directly regulated AQP2 expression by targeting 3'UTR of AQP2. These finding suggest that ZWT may reduce renal edema in Adriamycin-induced nephropathy via regulating AQP2 and miR-92b.