{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:29:16Z","timestamp":1791253756747,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T00:00:00Z","timestamp":1268611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Growth differentiation factor 15 (GDF15) is induced during heart failure development, and may influence different processes in cardiac remodeling. While its anti\u2010apoptotic action under conditions of ischemia\u2013reperfusion have been shown, it remained unclear if this is a broadly protective effect applicable to other apoptotic stimuli. Furthermore, effects on cardiac hypertrophy remained obscure. Therefore, we investigated the effects of GDF15 on induction of hypertrophy and apoptosis in ventricular cardiomyocytes. GDF15 (3\u2009ng\/ml) enhanced hypertrophic growth of cardiomyocytes as determined by an increase in cell size by 27\u2009\u00b1\u20095% and rate of protein synthesis by 47\u2009\u00b1\u200915%. In addition, a time and dose\u2010dependent increase in SMAD\u2010binding affinity was found, as well as enhanced phosphorylation of R\u2010SMAD1. Inhibition of SMADs by transformation of cardiomyocytes with SMAD\u2010decoy oligonucleotides abolished the hypertrophic growth effect. Specific inhibitors of PI3K (10\u2009\u00b5M LY290042 or 10\u2009nM wortmannin) or ERK (10\u2009\u00b5M PD98059) also blocked GDF15\u2010induced hypertrophy and SMAD activation. Apoptosis induction by three different agents, 100\u2009nM angiotensin II, 1\u2009ng\/ml TGF\u03b2<jats:sub>1<\/jats:sub>, or the NO\u2010donor SNAP (100\u2009\u00b5M) was blocked by addition of GDF15 (3\u2009ng\/ml). Scavenging of SMADs by transformation of cardiomyocytes with SMAD\u2010decoy oligonucleotides abolished the anti\u2010apoptotic effect of GDF15. In conclusion, GDF15 protects ventricular cardiomyocytes against different apoptotic stimuli and enhances hypertrophic growth. Hypertrophic signaling is thereby mediated via the kinases PI3K and ERK and the transcription factor R\u2010SMAD1. Thus, GDF15 may influence cardiac remodeling via two different mechanisms, apoptosis protection and induction of hypertrophy. J. Cell. Physiol. 224:120\u2013126, 2010 \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22102","type":"journal-article","created":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T15:09:33Z","timestamp":1268665773000},"page":"120-126","source":"Crossref","is-referenced-by-count":109,"title":["Growth differentiation factor 15 acts anti\u2010apoptotic and pro\u2010hypertrophic in adult cardiomyocytes"],"prefix":"10.1002","volume":"224","author":[{"given":"J.","family":"Heger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Schiegnitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"von Waldthausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.M.","family":"Anwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.M.","family":"Piper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Euler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,3,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.07.007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198512053132305"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0902"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101463200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000202805.73038.48"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.04.091"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.490946"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1993.1053"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(82)90171-7"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.04.030"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240100710"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)01065-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00171-0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.5.H1655"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.02.021"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0090-0"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199907)180:1<1::AID-JCP1>3.0.CO;2-V"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-005-0622-7"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0353fje"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000185833.42544.06"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.5.1616"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.650846"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-0990-y"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000202804.84885.d0"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000120704.97934.41"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.22102","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.22102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T11:04:14Z","timestamp":1721732654000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.22102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,15]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,7]]}},"alternative-id":["10.1002\/jcp.22102"],"URL":"https:\/\/doi.org\/10.1002\/jcp.22102","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,15]]}}}