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Methyl-CpG-binding domain protein 2 (MBD2), a protein readers of methylation, was used to analyze the impact of DNA methylation on vancomycin (VAN)-induced AKI. Here, in cultured human kidney tubular epithelial cells (HK-2), we show that knockdown of MBD2 by siRNA attenuated VAN-induced apoptosis, caspase activity, and the expression of BAX and cleaved caspase 3. Interestingly, knockdown of MBD2 by siRNA was associated with the suppression of miR-301a-5p. Mechanistic studies confirmed MBD2 binds to these methylated CpG elements of miR-301a-5p promoter, and then activates miR-301a-5p promoter by suppressing methylation. Furthermore, anti-miR-301a-5p significantly blocked VAN-induced apoptosis and caspase activity in HK-2 cells, which was accompanied by downregulation of p53, and upregulation of MITF, HDGF and MDM-4 together. The latter genes were further identified as target genes of miR-301a-5p, and silencing of MDM-4 promoted p53 accumulation. <jats:italic>In vivo<\/jats:italic>, mice with MBD2 knockout (MBD2-KO) were counteracted to VAN-induced AKI, indicated by the analysis of renal function, histology, apoptosis and inflammation. MBD2-KO also significantly suppressed the expression of miR-301a-5p, p53, BAX and cleaved caspase 3, and restored the expression of MDM-4, MITF and HDGF. Finally, <jats:italic>in vivo<\/jats:italic> inhibition of miR-301a-5p also ameliorated VAN-induced AKI. Together, these results show the novel MBD2\/miR-301a-5p\/MITF, HDGF and MDM-4\/p53 pathway in VAN-induced AKI.<\/jats:p>","DOI":"10.1038\/cddis.2017.509","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T12:43:02Z","timestamp":1507812182000},"page":"e3120-e3120","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["MBD2 upregulates miR-301a-5p to induce kidney cell apoptosis during vancomycin-induced AKI"],"prefix":"10.1038","volume":"8","author":[{"given":"Juan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangfa","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,12]]},"reference":[{"key":"BFcddis2017509_CR1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.jinf.2014.01.001","volume":"68","author":"Y Meije","year":"2014","unstructured":"Meije Y, Almirante B, Del Pozo JL, Martin MT, Fernandez-Hidalgo N, Shan A et al. 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