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Molecular Medicine

, Volume 16, Issue 9–10, pp 409–416 | Cite as

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 Article

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.

Notes

Acknowledgments

The study was supported in part by the National Institutes of Health and Department of Veterans Affairs. K Bhatt was supported by a predoctoral fellowship from the American Heart Association.

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Copyright information

© The Feinstein Institute for Medical Research 2010

Authors and Affiliations

  • Kirti Bhatt
    • 1
  • Li Zhou
    • 4
  • Qing-Sheng Mi
    • 4
  • Shuang Huang
    • 2
  • Jin-Xiong She
    • 3
  • Zheng Dong
    • 1
  1. 1.Department of Cellular Biology and AnatomyMedical College of Georgia and Charlie Norwood VA Medical CenterAugustaUSA
  2. 2.Department of BiochemistryMedical College of Georgia and Charlie Norwood VA Medical CenterAugustaUSA
  3. 3.Department of Center for Biotechnology and Genomic MedicineMedical College of Georgia and Charlie Norwood VA Medical CenterAugustaUSA
  4. 4.Departments of Dermatology and Internal MedicineHenry Ford Health SystemDetroitUSA

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