{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:09:07Z","timestamp":1787015347401,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T00:00:00Z","timestamp":1541635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Organ toxicity, including kidney injury, limits the use of cisplatin for the treatment of multiple human cancers. Hence, interventions to alleviate cisplatin\u2010induced nephropathy are of benefit to cancer patients. Recent studies have demonstrated that pharmacological inhibition of the Notch signaling pathway enhances cisplatin efficacy against several cancer cells. However, whether augmentation of the anti\u2010cancer effect of cisplatin by Notch inhibition comes at the cost of increased kidney injury is unclear. We show here that treatment of mice with cisplatin resulted in a significant increase in Notch ligand Delta\u2010like 1 (Dll1) and Notch1 intracellular domain (N1\n                    <jats:styled-content style=\"fixed-case\">ICD<\/jats:styled-content>\n                    ) protein expression levels in the kidneys. N\u2010[N\u2010(3,5\u2010difluorophenacetyl)\u2010L\u2010alanyl]\u2010S\u2010phenylglycine t\u2010butyl ester (\n                    <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content>\n                    ), a\n                    <jats:italic>\u03b3<\/jats:italic>\n                    \u2010secretase inhibitor reversed cisplatin\u2010induced increase in renal N1\n                    <jats:styled-content style=\"fixed-case\">ICD<\/jats:styled-content>\n                    expression and plasma or urinary levels of predictive biomarkers of acute kidney injury (\n                    <jats:styled-content style=\"fixed-case\">AKI<\/jats:styled-content>\n                    ).\n                    <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content>\n                    also mitigated cisplatin\u2010induced tubular injury and reduction in glomerular filtration rate. Real\u2010time multiphoton microscopy revealed marked necrosis and peritubular vascular dysfunction in the kidneys of cisplatin\u2010treated mice which were abrogated by\n                    <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content>\n                    . Cisplatin\u2010induced Dll1\/Notch1 signaling was recapitulated in a human proximal tubule epithelial cell line (\n                    <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n                    \u20102). si\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    \u2010mediated Dll1 knockdown and\n                    <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content>\n                    attenuated cisplatin\u2010induced Notch1 cleavage and cytotoxicity in\n                    <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>\n                    \u20102 cells. These data suggest that Dll1\u2010mediated Notch1 signaling contributes to cisplatin\u2010induced\n                    <jats:styled-content style=\"fixed-case\">AKI<\/jats:styled-content>\n                    . Hence, the Notch signaling pathway could be a potential therapeutic target to alleviate renal complications associated with cisplatin chemotherapy.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.13926","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T09:02:18Z","timestamp":1541667738000},"page":"260-270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["\u03b3\u2010secretase inhibitor\n                    <scp>DAPT<\/scp>\n                    mitigates cisplatin\u2010induced acute kidney injury by suppressing Notch1 signaling"],"prefix":"10.1111","volume":"23","author":[{"given":"Hitesh","family":"Soni","sequence":"first","affiliation":[{"name":"Department of Physiology University of Tennessee Health Science Center Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anberitha 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