MicroRNA-34a Is Induced via p53 during Cisplatin Nephrotoxicity and Contributes to Cell Survival
MicroRNA-34a Is Induced via p53 during Cisplatin Nephrotoxicity and Contributes to Cell Survival
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DOI：
10.2119/molmed.2010.00002
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发表时间：
2010-09-01
影响因子：
5.7
通讯作者：
Dong, Zheng
中科院分区：
文献类型：
--
作者：
Bhatt, Kirti;Zhou, Li;Dong, Zheng
microRNA是内源性产生的小的非编码RNA，并且已经成为病理生理条件如发育和肿瘤发生的重要调节剂。本研究通过北方印迹和实时荧光定量聚合酶链反应分析，检测了顺铂诱导的阿基和肾毒性实验模型中microRNA-34 a（miR-34 a）的表达。在培养的细胞中，miR-34 a在几小时内被诱导。在小鼠中，在顺铂处理1天后，在肾组织中可检测到miR-34 a诱导，并且在第3天增加至对照的约4倍。在顺铂处理期间，p53被激活，用匹非亭-α抑制p53消除了近端肾小管细胞的顺铂处理期间miR-34 a的诱导。在体内，顺铂对miR-34 a的诱导作用在p53缺陷小鼠中被消除，这一结果进一步证实了顺铂肾毒性期间p53在miR-34 a诱导中的作用。在功能上，miR-34 a与特异性反义寡核苷酸的拮抗作用增加了顺铂治疗期间的细胞死亡。总的来说，结果表明，miR-34 a在顺铂肾毒性期间通过p53诱导，并且可能对细胞存活发挥细胞保护作用（C）2010 The Feinstein Institute for Medical Research，www.feinsteininstitute.org
MicroRNAs are small noncoding RNAs that are produced endogenously and have emerged as important regulators in pathophysiological conditions such as development and tumorigenesis Very little is known about the regulation of microRNAs in renal diseases, including acute kidney injury (AKI). In this study, we examined the regulation of microRNA-34a (miR-34a) in experimental models of cisplatin-induced AKI and nephrotoxicity By Northern blot and real-time polymerase chain reaction analyses, we detected an induction of miR-34a in vitro during cisplatin treatment of mouse proximal tubular cells and also in vivo during cisplatin nephrotoxicity in C57BL/6 mice. In cultured cells, miR-34a was induced within a few hours In mice, miR-34a induction was detectable in renal tissues after 1 d of cisplatin treatment and increased to approximately four-fold of control at d 3. During cisplatin treatment, p53 was activated Inhibition of p53 with pifithrin-alpha abrogated the induction of miR-34a during cisplatin treatment of proximal tubular cells. In vivo, miR-34a induction by cisplatin was abrogated in p53-deficient mice, a result that further confirms a role for p53 in miR-34a induction during cisplatin nephrotoxicity. Functionally, antagonism of miR-34a with specific antisense oligonucleotides increased cell death during cisplatin treatment Collectively, the results suggest that miR-34a is induced via p53 during cisplatin nephrotoxicity and may play a cytoprotective role for cell survival (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org