{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:27:35Z","timestamp":1785472055633,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T00:00:00Z","timestamp":1545868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870475"],"award-info":[{"award-number":["81870475"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570646"],"award-info":[{"award-number":["81570646"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770951"],"award-info":[{"award-number":["81770951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500756"],"award-info":[{"award-number":["81500756"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009993","name":"Excellent Youth Foundation of Heilongjiang Province of China","doi-asserted-by":"publisher","award":["2017JJ1035"],"award-info":[{"award-number":["2017JJ1035"]}],"id":[{"id":"10.13039\/501100009993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recent studies have shown that autophagy exhibits a renoprotective role in various models of acute kidney injury (AKI). However, its role in vancomycin (Van)\u2010induced AKI remains largely unclarified. This study was the first to indicate that autophagy was rapidly activated in both human kidney\u20102 cells and renal tissues, and mammalian target of rapamycin (mTOR) was inactivated\n                    <jats:italic>via<\/jats:italic>\n                    the suppression of ERK1\/2 and mTOR during Van treatment. Interestingly, for both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments, the suppression of autophagy\n                    <jats:italic>via<\/jats:italic>\n                    chloroquine and PT\u2010Atg7\u2010KO significantly ameliorated Van\u2010induced kidney injury and renal tubular cell apoptosis. Global gene expression analysis indicated that the expression levels of 6159 genes were induced by Van treatment in the kidney cortical tissues of PT\u2010Atg7 wild\u2010type mice, and 18 of them were notably suppressed in PT\u2010Atg7\u2010KO mice. These 18 genes were further classified as programmed cell death, protein binding, signal transduction, E3 ubiquitin ligase, nucleoside diphosphate kinase activity, and E1\u2010like activating enzyme. Unexpectedly, following Van treatment, PKC\u2010\u03b4 expression was found to be highest among the 4 genes related to cell death, which was remarkably suppressed\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in PT\u2010Atg7\u2010KO mice. In addition, Atg7 could induce renal cell apoptosis during Van treatment\n                    <jats:italic>via<\/jats:italic>\n                    binding to PKC\u2010\u03b4. Likewise, the inhibition of PKC\u03b4 ameliorated Van\u2010induced apoptosis in human kidney\u20102 cells and kidney tissues. Furthermore, the data showed that PT\u2010Atg7\u2010KO exerted a renoprotective effect against Van\u2010induced nephrotoxicity, but this effect was lost after injection with myc\u2010tagged PKC\u03b4. Taken altogether, these results indicate that Van induces autophagy by suppressing the activation of the ERK1\/2 and mTOR signaling pathway. In addition, Atg7 mediates Van\u2010induced AKI through the activation of PKC\u03b4. In sum, autophagy inhibition may serve as a novel therapeutic target for treating nephrotoxic AKI induced by Van.\u2014Xu, X., Pan, J., Li, H., Li, X., Fang, F., Wu, D., Zhou, Y., Zheng, P., Xiong, L., Zhang, D. Atg7 mediates renal tubular cell apoptosis in vancomycin nephrotoxicity through activation of PKC\u2010\u03b4. FASEB J. 33, 4513\u20134524 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801515r","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T13:54:52Z","timestamp":1545918892000},"page":"4513-4524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Atg7 mediates renal tubular cell apoptosis in vancomycin nephrotoxicity through activation of PKC\u2010\u03b4"],"prefix":"10.1096","volume":"33","author":[{"given":"Xuan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Central 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