{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:55:47Z","timestamp":1790304947256,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI14C3417"],"award-info":[{"award-number":["HI14C3417"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI16C1641"],"award-info":[{"award-number":["HI16C1641"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"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\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2015R1A1A3A04000946"],"award-info":[{"award-number":["NRF-2015R1A1A3A04000946"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2018R1D1A1A02043014"],"award-info":[{"award-number":["NRF-2018R1D1A1A02043014"]}],"id":[{"id":"10.13039\/501100003621","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":[[2019,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recently, we showed that tacrolimus\u2010induced renal injury was closely associated with impairment of autophagy clearance, and Klotho deficiency aggravated tacrolimus\u2010induced renal injury. In this study, we evaluated the effect of Klotho treatment on autophagy clearance in tacrolimus\u2010induced renal injury. We evaluated the effect of Klotho on tacrolimus\u2010induced renal injury in an experimental mouse model and\n                    <jats:italic>in vitro<\/jats:italic>\n                    by treatment with tacrolimus and\/or recombinant mouse Klotho.\n                    <jats:italic>In vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies showed that tacrolimus treatment impaired lysosomal acidification and decreased cathepsin B activity, expression of lysosome\u2010associated membrane protein 2, and expression of transcription factor EB (TFEB), a master regulator for lysosomal biogenesis. These results were improved by Klotho treatment. Moreover, addition of bafilomycin A1, an inhibitor of lysosomal function, abolished the protective effect of Klotho, indicating that the protective effect of Klotho was closely associated with lysosome function. Klotho induced nuclear translocation of TFEB through inhibition of phosphorylation of glycogen synthase kinase 3\u03b2 (GSK3\u03b2) by confirming using CHIR99021, a GSK3\u03b2 inhibitor. Collectively, our data suggest that Klotho improves autophagy clearance\n                    <jats:italic>via<\/jats:italic>\n                    activation of lysosomal function in tacrolimus\u2010induced nephrotoxicity.\u2014Lim, S. W., Shin, Y. J., Luo, K., Quan, Y., Ko, E. J., Chung, B. H., Yang, C. W. Effect of Klotho on autophagy clearance in tacrolimus\u2010induced renal injury. FASEB J. 33, 2694\u20132706 (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.201800751r","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T14:02:04Z","timestamp":1539266524000},"page":"2694-2706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Effect of Klotho on autophagy clearance in tacrolimus\u2010induced renal injury"],"prefix":"10.1096","volume":"33","author":[{"given":"Sun Woo","family":"Lim","sequence":"first","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Luo","sequence":"additional","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Quan","sequence":"additional","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jeong","family":"Ko","sequence":"additional","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"},{"name":"Division of Nephrology Department of Internal Medicine Seoul St. Mary's Hospital College of Medicine Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Ha","family":"Chung","sequence":"additional","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"},{"name":"Division of Nephrology Department of Internal Medicine Seoul St. Mary's Hospital College of Medicine Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Woo","family":"Yang","sequence":"additional","affiliation":[{"name":"Convergent Research Consortium for Immunologic Disease Seoul St. Mary's Hospital Catholic University of Korea Seoul South Korea"},{"name":"Transplant Research Center Catholic University of Korea Seoul South Korea"},{"name":"Division of Nephrology Department of Internal Medicine Seoul St. Mary's Hospital College of Medicine Catholic University of Korea Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00099-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.27.421"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1717"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2161"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000351648"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"29921","DOI":"10.1038\/srep29921","article-title":"Effect of exendin-4 on autophagy clearance in beta cell of rats with tacrolimus-induced diabetes mellitus","volume":"6","author":"Lim S. W.","year":"2016","journal-title":"Sci Rep."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.75"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/36285"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112766"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1159\/000446447","article-title":"Klotho deficiency aggravates tacrolimus-induced renal injury via the phosphatidylinositol 3-kinase-Akt-forkhead box protein O pathway","volume":"43","author":"Jin J.","year":"2016","journal-title":"Am. J. Nephrol."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.365"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2016.3437"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3389\/fphar.2017.00499","article-title":"Hydrogen-rich saline alleviates kidney fibrosis following AKI and retains Klotho expression","volume":"8","author":"Chen J.","year":"2017","journal-title":"Front. Pharmacol."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00353"},{"key":"e_1_2_9_16_1","first-page":"295","article-title":"Klotho regulates cigarette smoke-induced autophagy: implication in pathogenesis of COPD","volume":"195","author":"Li L.","year":"2017","journal-title":"Hai"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4420"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082968"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.11.016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0201"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1159\/000488172","article-title":"Klotho reduces necroptosis by targeting oxidative stress involved in renal ischemic-reperfusion injury","volume":"45","author":"Qian Y.","year":"2018","journal-title":"Cell Physiol Biochem."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.07.024"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204592"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"142521","DOI":"10.1155\/2015\/142521","article-title":"Proximal tubular injury in medullary rays is an rarly sign of acute tacrolimus nephrotoxicity","volume":"2015","author":"Cosner D.","year":"2015","journal-title":"J. Transplant."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.04.026"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.9.16465"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010070705"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.24.10263"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174447"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.11.17166"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.616714"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr309"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-011-0950-5"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181e117b4"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201800751R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201800751R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201800751R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:15:39Z","timestamp":1761700539000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201800751R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,11]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1096\/fj.201800751R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201800751r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,11]]},"assertion":[{"value":"2018-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}