{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:49:36Z","timestamp":1784771376652,"version":"3.55.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Basic Science Research Program"},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007431","name":"NRF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["NRF-2017R1A2A2A05001197"],"award-info":[{"award-number":["NRF-2017R1A2A2A05001197"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["NRF-2019R1A2C1090358"],"award-info":[{"award-number":["NRF-2019R1A2C1090358"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomedical Research Institute"},{"name":"Jeonbuk National University Hospital","award":["CUHBRI-2012-02-003"],"award-info":[{"award-number":["CUHBRI-2012-02-003"]}]},{"name":"Basic Science Research Program"},{"DOI":"10.13039\/100009122","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2017R1A6A3A11029375"],"award-info":[{"award-number":["NRF-2017R1A6A3A11029375"]}],"id":[{"id":"10.13039\/100009122","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Activation of mitogen-activated protein kinase phosphatase-1 (MKP-1), a dual-specificity protein phosphatase, regulates mitogen-activated protein kinase signaling. C-Jun N-terminal kinase (JNK) and p38 are activated in cisplatin-induced renal injury. However, the change of MKP-1 expression in cisplatin-induced renal injury and the regulatory effect of sirtuin 2 (SIRT2), a nicotinamide adenine dinucleotide\u2013dependent deacetylase, on MKP-1 remains unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To address these issues, we used constitutional Sirt2 knockout (KO) mice, transgenic (TG) mice with increased expression of SIRT2 specifically in proximal tubular epithelial cellsand wild-type (WT) mice. Cisplatin nephrotoxicity was induced by intraperitoneal injection of cisplatin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>MKP-1 expression in the kidney was decreased after cisplatin treatment. Cisplatin-induced downregulation of MKP-1 was reversed in Sirt2 KO mice kidney and further decreased in Sirt2 TG mice kidney. We observed similar phenomenon with SIRT2-knockdown or SIRT2-overexpressed tubular epithelial cells. Phosphorylation of p38 and JNK, a downstream signal pathway of MKP-1, increased in WT mice kidney following treatment with cisplatin. A decrease in SIRT2 suppressed cisplatin-induced phosphorylation of p38 and JNK in kidney and tubular epithelial cells. Overexpression of SIRT2 further increased phosphorylation of p38 and JNK in kidney and tubular epithelial cells. Acetylation of MKP-1 was significantly increased in SIRT2-knockdown cells and decreased in SIRT2-overexpressed cells after cisplatin stimulation. Sirt2 KO mice and Sirt2 TG mice showed amelioration and aggravation of renal injury, apoptosis, necroptosis and inflammation induced by cisplatin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data show that SIRT2 is associated with cisplatin-induced renal injury through regulation of MKP-1 expression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfaa042","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T20:13:24Z","timestamp":1581538404000},"page":"1145-1156","source":"Crossref","is-referenced-by-count":48,"title":["SIRT2 is involved in cisplatin-induced acute kidney injury through regulation of mitogen-activated protein kinase phosphatase-1"],"prefix":"10.1093","volume":"35","author":[{"given":"Yu Jin","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Chonbuk National University Medical School, Jeonju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Chonbuk National University Medical School, Jeonju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Pyo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Chonbuk National University Medical School, Jeonju, Republic of Korea"},{"name":"Research Institute of Clinical Medicine of Jeonbuk\u00a0National University-Biomedical Research Institute of Jeonbuk\u00a0National University Hospital, Jeonju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Chonbuk National University Medical School, Jeonju, Republic of Korea"},{"name":"Research Institute of Clinical Medicine of Jeonbuk\u00a0National University-Biomedical Research Institute of Jeonbuk\u00a0National University Hospital, Jeonju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"2020081014165533600_gfaa042-B1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1124\/pr.107.00106","article-title":"Mitogen-activated protein (MAP) kinase\/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer","volume":"60","author":"Boutros","year":"2008","journal-title":"Pharmacol Rev"},{"key":"2020081014165533600_gfaa042-B2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/bcpt.12141","article-title":"Mitogen-activated protein kinase phosphatase 1 as an inflammatory factor and drug target","volume":"114","author":"Korhonen","year":"2014","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"2020081014165533600_gfaa042-B3","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1517\/14728222.2010.528395","article-title":"Mitogen-activated protein kinase phosphatase-1\u2014a potential therapeutic target in metabolic disease","volume":"14","author":"Roth Flach","year":"2010","journal-title":"Expert Opin Ther Targets"},{"key":"2020081014165533600_gfaa042-B4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s10555-008-9123-1","article-title":"Dual-specificity MAP kinase phosphatases (MKPs) and cancer","volume":"27","author":"Keyse","year":"2008","journal-title":"Cancer Metastasis Rev"},{"key":"2020081014165533600_gfaa042-B5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10555-010-9208-5","article-title":"The role of MAP kinases and MAP kinase phosphatase-1 in resistance to breast cancer treatment","volume":"29","author":"Haagenson","year":"2010","journal-title":"Cancer Metastasis Rev"},{"key":"2020081014165533600_gfaa042-B6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1096\/fasebj.14.1.6","article-title":"Dual specificity phosphatases: a gene family for control of MAP kinase function","volume":"14","author":"Camps","year":"2000","journal-title":"FASEB J"},{"key":"2020081014165533600_gfaa042-B7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12931-017-0637-3","article-title":"Role and regulation of MKP-1 in airway inflammation","volume":"18","author":"Moosavi","year":"2017","journal-title":"Respir Res"},{"key":"2020081014165533600_gfaa042-B8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.freeradbiomed.2017.03.020","article-title":"Mitogen-activated protein kinase phosphatase 1 (MKP-1) in macrophage biology and cardiovascular disease. A redox-regulated master controller of monocyte function and macrophage phenotype","volume":"109","author":"Kim","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"2020081014165533600_gfaa042-B9","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1681\/ASN.2014030226","article-title":"SIRT2 regulates LPS-induced renal tubular CXCL2 and CCL2 expression","volume":"26","author":"Jung","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2020081014165533600_gfaa042-B10","first-page":"511","article-title":"Protein extracted from\u00a0Porphyra yezoensis\u00a0prevents cisplatin-induced nephrotoxicity by downregulating the MAPK and NF-\u03ba B pathways","volume":"41","author":"Kim","year":"2018","journal-title":"Int J Mol Med"},{"key":"2020081014165533600_gfaa042-B11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2131\/jts.41.339","article-title":"Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways","volume":"41","author":"Thongnuanjan","year":"2016","journal-title":"J Toxicol Sci"},{"key":"2020081014165533600_gfaa042-B12","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1084\/jem.20071728","article-title":"Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling","volume":"205","author":"Cao","year":"2008","journal-title":"J Exp Med"},{"key":"2020081014165533600_gfaa042-B13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1365-2443.2005.00836.x","article-title":"Role of NAD-dependent deacetylases SIRT1 and SIRT2 in radiation and cisplatin-induced cell death in vertebrate cells","volume":"10","author":"Matsushita","year":"2005","journal-title":"Genes Cells"},{"key":"2020081014165533600_gfaa042-B14","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.bbrc.2012.01.148","article-title":"SIRT1 overexpression decreases cisplatin-induced acetylation of NF-\u03ba B p65 subunit and cytotoxicity in renal proximal tubule cells","volume":"419","author":"Jung","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"2020081014165533600_gfaa042-B15","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1681\/ASN.2008111204","article-title":"siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury","volume":"20","author":"Molitoris","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2020081014165533600_gfaa042-B16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.23876\/j.krcp.18.0114","article-title":"The role of senescence of bone marrow cells in acute kidney injury","volume":"38","author":"Lee","year":"2019","journal-title":"Kidney Res Clin Pract"},{"key":"2020081014165533600_gfaa042-B17","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1681\/ASN.2014080741","article-title":"A role for tubular necroptosis in cisplatin-induced AKI","volume":"26","author":"Xu","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2020081014165533600_gfaa042-B18","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.2337\/diabetes.52.10.2586","article-title":"Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes","volume":"52","author":"Okada","year":"2003","journal-title":"Diabetes"},{"key":"2020081014165533600_gfaa042-B19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1023\/A:1007029409521","article-title":"Regulation of ICAM-1 expression in mouse macrophages","volume":"24","author":"Hubbard","year":"2000","journal-title":"Inflammation"},{"key":"2020081014165533600_gfaa042-B20","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1124\/mol.104.003400","article-title":"Evidence that mitogen-activated protein kinase phosphatase-1 induction by proteasome inhibitors plays an antiapoptotic role","volume":"66","author":"Small","year":"2004","journal-title":"Mol Pharmacol"},{"key":"2020081014165533600_gfaa042-B21","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/01.ju.0000124990.37563.00","article-title":"Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells","volume":"172","author":"Mizuno","year":"2004","journal-title":"J Urol"},{"key":"2020081014165533600_gfaa042-B22","doi-asserted-by":"crossref","first-page":"5939","DOI":"10.1038\/onc.2017.197","article-title":"MKP-1 suppresses PARP-1 degradation to mediate cisplatin resistance","volume":"36","author":"Wang","year":"2017","journal-title":"Oncogene"},{"key":"2020081014165533600_gfaa042-B23","doi-asserted-by":"crossref","first-page":"8870","DOI":"10.1158\/0008-5472.CAN-06-1280","article-title":"Mitogen-activated protein kinase phosphatase-1 is required for cisplatin resistance","volume":"66","author":"Wang","year":"2006","journal-title":"Cancer Res"},{"key":"2020081014165533600_gfaa042-B24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1523-1755.2000.00137.x","article-title":"Expression of mitogen-activated protein kinase family in rat renal development","volume":"58","author":"Omori","year":"2000","journal-title":"Kidney Int"},{"key":"2020081014165533600_gfaa042-B25","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1124\/jpet.114.213769","article-title":"The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury","volume":"349","author":"Kim","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"key":"2020081014165533600_gfaa042-B26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cbi.2013.08.009","article-title":"Modulation of albumin-induced endoplasmic reticulum stress in renal proximal tubule cells by upregulation of MAPK phosphatase-1","volume":"206","author":"Gorostizaga","year":"2013","journal-title":"Chem Biol Interact"},{"key":"2020081014165533600_gfaa042-B27","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/jcp.20909","article-title":"ERK1\/2-driven and MKP-mediated inhibition of EGF-induced ERK5 signaling in human proximal tubular cells","volume":"211","author":"Sarkozi","year":"2007","journal-title":"J Cell Physiol"},{"key":"2020081014165533600_gfaa042-B28","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1128\/MCB.25.11.4792-4803.2005","article-title":"The noncatalytic amino terminus of mitogen-activated protein kinase phosphatase 1 directs nuclear targeting and serum response element transcriptional regulation","volume":"25","author":"Wu","year":"2005","journal-title":"Mol Cell Biol"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/7\/1145\/33636488\/gfaa042.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/7\/1145\/33636488\/gfaa042.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T19:33:21Z","timestamp":1597088001000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/35\/7\/1145\/5815250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,2]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4,2]]},"published-print":{"date-parts":[[2020,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfaa042","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7]]},"published":{"date-parts":[[2020,4,2]]}}}