title: p53 activates miR-192-5p to mediate vancomycin induced AKI.
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.
authors.affiliation: Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of cellular Biology and anatomy, Medical college of Georgia at Georgia Regents University; Charlie Norwood VA Medical Center, Augusta, GA, USA.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xiang
authors.affiliation: Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Dongshan
authors.initials: D
authors.lastname: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D052160:Benzothiazoles / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D016158:Genes, p53; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D035683:MicroRNAs; C539618:Mirn192 microRNA, mouse; D016159:Tumor Suppressor Protein p53; D014050:Toluene; D014640:Vancomycin; C121565:pifithrin