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.