p53 activates miR-192-5p to mediate vancomycin induced AKI

Jinwen Chen, Juan Wang, Huiling Li, Shixuan Wang, Xudong Xiang, Dongshan Zhang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Pathogenic role of p53 in AKI remains controversial and the underlying mechanism is unclear. Here, we tested whether the inhibition of p53 may ameliorate vancomycin (VAN) induced acute kidney injury (AKI). Mice with p53 knock out (p53-KO) were resistant to VAN induced AKI, indicated by the analysis of renal function, histology, and apoptosis. Mechanistically, AKI was associated with the upregulation of several known p53 target genes, including Bax and p21, and this association was attenuated in p53-KO mice. Furthermore, the expression of miR-192-5p was significantly decreased in the p53-KO kidney tissues. In human renal tubular epithelial cell line (HK-2), VAN induced p53 accumulation and miR-192-5p expression. Both apoptosis of HK-2 cells and expression of miR-192-5p were also suppressed by pifithrin-α. Anti-miR-192-5p significantly blocked VAN-induced apoptosis and caspase activity in HK-2 cells. Consistently, in vivo inhibition of miR-192-5p also suppressed VAN induced AKI. Thus, we provided clinical and genetic evidence that p53 was associated with the development of VAN induced AKI through upregulation of miR-192-5p.

Original languageEnglish (US)
Article number38868
JournalScientific Reports
Volume6
DOIs
StatePublished - Dec 12 2016

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Vancomycin
Acute Kidney Injury
Apoptosis
Kidney
Up-Regulation
p53 Genes
Caspases
Knockout Mice
Histology
Epithelial Cells
Cell Line

ASJC Scopus subject areas

  • General

Cite this

p53 activates miR-192-5p to mediate vancomycin induced AKI. / Chen, Jinwen; Wang, Juan; Li, Huiling; Wang, Shixuan; Xiang, Xudong; Zhang, Dongshan.

In: Scientific Reports, Vol. 6, 38868, 12.12.2016.

Research output: Contribution to journalArticle

Chen, Jinwen ; Wang, Juan ; Li, Huiling ; Wang, Shixuan ; Xiang, Xudong ; Zhang, Dongshan. / p53 activates miR-192-5p to mediate vancomycin induced AKI. In: Scientific Reports. 2016 ; Vol. 6.
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