MicroRNA-34a is induced via p53 during cisplatin nephrotoxicity and contributes to cell survival

Kirti Bhatt, Li Zhou, Qing Sheng Mi, Shuang Huang, Jin-Xiong She, Zheng Dong

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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-α 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.

Original languageEnglish (US)
Pages (from-to)409-416
Number of pages8
JournalMolecular Medicine
Volume16
Issue number9-10
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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