{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:10:51Z","timestamp":1790136651079,"version":"4.0.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T00:00:00Z","timestamp":1516147200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400299"],"award-info":[{"award-number":["81400299"]}],"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":["81370446"],"award-info":[{"award-number":["81370446"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["In Vitro Cell.Dev.Biol.-Animal"],"published-print":{"date-parts":[[2018,3]]},"DOI":"10.1007\/s11626-017-0215-5","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T10:06:28Z","timestamp":1516183588000},"page":"250-256","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Klotho attenuates isoproterenol-induced hypertrophic response in H9C2 cells by activating Na+\/K+-ATPase and inhibiting the reverse mode of Na+\/Ca2+-exchanger"],"prefix":"10.1007","volume":"54","author":[{"given":"Gang","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-Shuang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8059-4694","authenticated-orcid":false,"given":"Liang-Yi","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"issue":"1","key":"215_CR1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/1471-2407-10-105","volume":"10","author":"V Askoxylakis","year":"2010","unstructured":"Askoxylakis V, Thieke C, Pleger ST, Most P, Tanner J, Lindel K, Katus HA, Debus J, Bischof M (2010) Long-term survival of cancer patients compared to heart failure and stroke: a systematic review. BMC Cancer 10(1):105. \n                    https:\/\/doi.org\/10.1186\/1471-2407-10-105","journal-title":"BMC Cancer"},{"issue":"1","key":"215_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/00005344-200501000-00003","volume":"45","author":"R Bos","year":"2005","unstructured":"Bos R, Mougenot N, Findji L, Mediani O, Vanhoutte PM, Lechat P (2005) Inhibition of catecholamine-induced cardiac fibrosis by an aldosterone antagonist. J Cardiovasc Pharmacol 45(1):8\u201313. \n                    https:\/\/doi.org\/10.1097\/00005344-200501000-00003","journal-title":"J Cardiovasc Pharmacol"},{"issue":"1","key":"215_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jchf.2012.10.002","volume":"1","author":"E Braunwald","year":"2013","unstructured":"Braunwald E (2013) Heart failure. JACC Heart failure 1(1):1\u201320. \n                    https:\/\/doi.org\/10.1016\/j.jchf.2012.10.002","journal-title":"JACC Heart failure"},{"issue":"4","key":"215_CR4","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1161\/CIRCULATIONAHA.113.001878","volume":"128","author":"JS Burchfield","year":"2013","unstructured":"Burchfield JS, Xie M, Hill JA (2013) Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation 128(4):388\u2013400. \n                    https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.113.001878","journal-title":"Circulation"},{"issue":"2","key":"215_CR5","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1161\/CIRCRESAHA.114.302293","volume":"114","author":"RN Correll","year":"2014","unstructured":"Correll RN, Eder P, Burr AR, Despa S, Davis J, Bers DM, Molkentin JD (2014) Overexpression of the Na+\/K+ ATPase alpha2 but not alpha1 isoform attenuates pathological cardiac hypertrophy and remodeling. Circ Res 114(2):249\u2013256. \n                    https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.302293","journal-title":"Circ Res"},{"issue":"1","key":"215_CR6","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.etap.2014.05.008","volume":"38","author":"H Dai","year":"2014","unstructured":"Dai H, Jia G, Liu X, Liu Z, Wang H (2014) Astragalus polysaccharide inhibits isoprenaline-induced cardiac hypertrophy via suppressing Ca(2)(+)-mediated calcineurin\/NFATc3 and CaMKII signaling cascades. Environ Toxicol Pharmacol 38(1):263\u2013271. \n                    https:\/\/doi.org\/10.1016\/j.etap.2014.05.008","journal-title":"Environ Toxicol Pharmacol"},{"issue":"4","key":"215_CR7","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1093\/cvr\/cvs213","volume":"95","author":"S Despa","year":"2012","unstructured":"Despa S, Lingrel JB, Bers DM (2012) Na(+)\/K)+)-ATPase alpha2-isoform preferentially modulates Ca2(+) transients and sarcoplasmic reticulum Ca2(+) release in cardiac myocytes. Cardiovasc Res 95(4):480\u2013486. \n                    https:\/\/doi.org\/10.1093\/cvr\/cvs213","journal-title":"Cardiovasc Res"},{"issue":"13","key":"215_CR8","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1161\/01.CIR.0000120390.68287.BB","volume":"109","author":"N Frey","year":"2004","unstructured":"Frey N, Katus HA, Olson EN, Hill JA (2004) Hypertrophy of the heart: a new therapeutic target? Circulation 109(13):1580\u20131589. \n                    https:\/\/doi.org\/10.1161\/01.CIR.0000120390.68287.BB","journal-title":"Circulation"},{"issue":"4","key":"215_CR9","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/S0008-6363(02)00810-6","volume":"57","author":"W Fuller","year":"2003","unstructured":"Fuller W, Parmar V, Eaton P, Bell JR, Shattock MJ (2003) Cardiac ischemia causes inhibition of the Na\/K ATPase by a labile cytosolic compound whose production is linked to oxidant stress. Cardiovasc Res 57(4):1044\u20131051. \n                    https:\/\/doi.org\/10.1016\/S0008-6363(02)00810-6","journal-title":"Cardiovasc Res"},{"issue":"3","key":"215_CR10","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.bbrc.2005.11.094","volume":"339","author":"M Ikushima","year":"2006","unstructured":"Ikushima M, Rakugi H, Ishikawa K, Maekawa Y, Yamamoto K, Ohta J, Chihara Y, Kida I, Ogihara T (2006) Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochem Biophys Res Commun 339(3):827\u2013832. \n                    https:\/\/doi.org\/10.1016\/j.bbrc.2005.11.094","journal-title":"Biochem Biophys Res Commun"},{"issue":"5831","key":"215_CR11","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1126\/science.1135901","volume":"316","author":"A Imura","year":"2007","unstructured":"Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T (2007) Alpha-Klotho as a regulator of calcium homeostasis. Science 316(5831):1615\u20131618. \n                    https:\/\/doi.org\/10.1126\/science.1135901","journal-title":"Science"},{"key":"215_CR12","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/S1097-2765(00)80349-4","volume":"3","author":"PF James","year":"1999","unstructured":"James PF, Grupp IL, Grupp G, Woo AL, Askew GR, Croyle ML, Walsh RA, Lingrel JB (1999) Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart. Mol Cell 3:555\u2013563","journal-title":"Mol Cell"},{"issue":"3","key":"215_CR13","first-page":"219","volume":"43","author":"Z Jia","year":"2015","unstructured":"Jia Z, Wei L, Liu Q, Zhu Z, Yang J, Yang X, Gan S, Chen W, Zhang L (2015) Impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure. Zhonghua Xin Xue Guan Bing Za Zhi 43(3):219\u2013226","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"issue":"6655","key":"215_CR14","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/36285","volume":"390","author":"M Kuro-o","year":"1997","unstructured":"Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390(6655):45\u201351. \n                    https:\/\/doi.org\/10.1038\/36285","journal-title":"Nature"},{"issue":"5742","key":"215_CR15","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1126\/science.1112766","volume":"309","author":"H Kurosu","year":"2005","unstructured":"Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M (2005) Suppression of aging in mice by the hormone Klotho. Science 309(5742):1829\u20131833. \n                    https:\/\/doi.org\/10.1126\/science.1112766","journal-title":"Science"},{"issue":"45","key":"215_CR16","doi-asserted-by":"publisher","first-page":"19308","DOI":"10.1073\/pnas.1008544107","volume":"107","author":"T Kusaba","year":"2010","unstructured":"Kusaba T, Okigaki M, Matui A, Murakami M, Ishikawa K, Kimura T, Sonomura K, Adachi Y, Shibuya M, Shirayama T, Tanda S, Hatta T, Sasaki S, Mori Y, Matsubara H (2010) Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci U S A 107(45):19308\u201319313. \n                    https:\/\/doi.org\/10.1073\/pnas.1008544107","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"215_CR17","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.2337\/diab.40.11.1560","volume":"40","author":"T Ohara","year":"1991","unstructured":"Ohara T, Sussman KE, Draznin B (1991) Effect of diabetes on cytosolic free Ca2+ and Na(+)-K(+)-ATPase in rat aorta. Diabetes 40(11):1560\u20131563. \n                    https:\/\/doi.org\/10.2337\/diab.40.11.1560","journal-title":"Diabetes"},{"key":"215_CR18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1093\/ndt\/gfm702","volume":"23","author":"MS Razzaque","year":"2008","unstructured":"Razzaque MS (2008) Klotho and Na+,K+-ATPase activity: solving the calcium metabolism dilemma? Nephrol Dial Transplant 23:459\u2013461","journal-title":"Nephrol Dial Transplant"},{"issue":"12","key":"215_CR19","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1161\/01.CIR.101.12.1441","volume":"101","author":"H Satoh","year":"2000","unstructured":"Satoh H, Ginsburg KS, Qing K, Terada H, Hayashi H, Bers DM (2000) KB-R7943 block of Ca(2+) influx via Na(+)\/Ca(2+) exchange does not alter twitches or glycoside inotropy but prevents Ca(2+) overload in rat ventricular myocytes. Circulation 101(12):1441\u20131446. \n                    https:\/\/doi.org\/10.1161\/01.CIR.101.12.1441","journal-title":"Circulation"},{"issue":"2","key":"215_CR20","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0008-6363(01)00282-6","volume":"51","author":"C Schafer","year":"2001","unstructured":"Schafer C, Ladilov Y, Inserte J, Schafer M, Haffner S, Garcia-Dorado D, Piper HM (2001) Role of the reverse mode of the Na+\/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury. Cardiovasc Res 51(2):241\u2013250. \n                    https:\/\/doi.org\/10.1016\/S0008-6363(01)00282-6","journal-title":"Cardiovasc Res"},{"issue":"16","key":"215_CR21","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1161\/CIRCULATIONAHA.115.013894","volume":"131","author":"GG Schiattarella","year":"2015","unstructured":"Schiattarella GG, Hill JA (2015) Inhibition of hypertrophy is a good therapeutic strategy in ventricular pressure overload. Circulation 131(16):1435\u20131447. \n                    https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.115.013894","journal-title":"Circulation"},{"key":"215_CR22","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.lfs.2015.05.024","volume":"135","author":"S Song","year":"2015","unstructured":"Song S, Si LY (2015) Klotho ameliorated isoproterenol-induced pathological changes in cardiomyocytes via the regulation of oxidative stress. Life Sci 135:118\u2013123. \n                    https:\/\/doi.org\/10.1016\/j.lfs.2015.05.024","journal-title":"Life Sci"},{"issue":"12","key":"215_CR23","doi-asserted-by":"publisher","first-page":"e82968","DOI":"10.1371\/journal.pone.0082968","volume":"8","author":"S Song","year":"2013","unstructured":"Song S, Gao P, Xiao H, Xu Y, Si LY (2013) Klotho suppresses cardiomyocyte apoptosis in mice with stress-induced cardiac injury via downregulation of endoplasmic reticulum stress. PLoS One 8(12):e82968. \n                    https:\/\/doi.org\/10.1371\/journal.pone.0082968","journal-title":"PLoS One"},{"issue":"1","key":"215_CR24","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ceca.2010.06.006","volume":"48","author":"F Swift","year":"2010","unstructured":"Swift F, Tovsrud N, Sjaastad I, Sejersted OM, Niggli E, Egger M (2010) Functional coupling of alpha(2)-isoform Na(+)\/K(+)-ATPase and Ca(2+) extrusion through the Na(+)\/Ca(2+)-exchanger in cardiomyocytes. Cell Calcium 48(1):54\u201360. \n                    https:\/\/doi.org\/10.1016\/j.ceca.2010.06.006","journal-title":"Cell Calcium"},{"issue":"2","key":"215_CR25","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s11626-010-9368-1","volume":"47","author":"SJ Watkins","year":"2011","unstructured":"Watkins SJ, Borthwick GM, Arthur HM (2011) The H9C2 cell line and primary neonatal cardiomyocyte cells show similar hypertrophic responses in vitro. In Vitro Cell Dev Biol Anim 47(2):125\u2013131. \n                    https:\/\/doi.org\/10.1007\/s11626-010-9368-1","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"215_CR26","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.bbrc.2011.02.013","volume":"406","author":"KY Xu","year":"2011","unstructured":"Xu KY, Zhu W, Chen L, DeFilippi C, Zhang J, Xiao RP (2011) Mechanistic distinction between activation and inhibition of (Na(+)+K(+))-ATPase-mediated Ca2+ influx in cardiomyocytes. Biochem Biophys Res Commun 406:200\u2013203","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"215_CR27","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1258\/ebm.2011.011273","volume":"237","author":"H Xu","year":"2012","unstructured":"Xu H, Zhang Y, Sun J, Wei J, Sun L, Zhang J (2012) Effect of distinct sources of Ca(2+) on cardiac hypertrophy in cardiomyocytes. Exp Biol Med (Maywood) 237(3):271\u2013278. \n                    https:\/\/doi.org\/10.1258\/ebm.2011.011273","journal-title":"Exp Biol Med (Maywood)"},{"issue":"43","key":"215_CR28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/nm1215","volume":"11","author":"R Zhang","year":"2005","unstructured":"Zhang R, Khoo MS, Wu Y, Yang Y, Grueter CE, Ni G, Price EE Jr, Thiel W, Guatimosim S, Song LS, Madu EC, Shah AN, Vishnivetskaya TA, Atkinson JB, Gurevich VV, Salama G, Lederer WJ, Colbran RJ, Anderson ME (2005) Calmodulin kinase II inhibition protects against structural heart disease. Nat Med 11(43):409\u2013417. \n                    https:\/\/doi.org\/10.1038\/nm1215","journal-title":"Nat Med"}],"container-title":["In Vitro Cellular &amp; Developmental Biology - Animal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11626-017-0215-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11626-017-0215-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11626-017-0215-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T20:15:12Z","timestamp":1547669712000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11626-017-0215-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,17]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["215"],"URL":"https:\/\/doi.org\/10.1007\/s11626-017-0215-5","relation":{},"ISSN":["1071-2690","1543-706X"],"issn-type":[{"value":"1071-2690","type":"print"},{"value":"1543-706X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,17]]},"assertion":[{"value":"12 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that there are no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}