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To determine whether TR3 is involved in the regulation of the pathological cardiac hypertrophy induced by AngII, we established mouse and rat hypertrophy models using chronic AngII administration. Our results reveal that a deficiency of TR3 in mice or the knockdown of TR3 in the left ventricle of rats attenuated AngII\u2010induced cardiac hypertrophy compared with the respective controls. A mechanistic analysis demonstrates that the TR3\u2010mediated activation of mTORC1 is associated with AngII\u2010induced cardiac hypertrophy. TR3 was shown to form a trimer with the TSC1\/TSC2 complex that specifically promoted TSC2 degradation via a proteasome\/ubiquitination pathway. As a result, mTORC1, but not mTORC2, was activated; this was accompanied by increased protein synthesis, enhanced production of reactive oxygen species and enlarged cell size, thereby resulting in cardiac hypertrophy. This study demonstrates that TR3 positively regulates cardiac hypertrophy by influencing the effect of AngII on the mTOR pathway. The elimination or reduction of TR3 may reduce cardiac hypertrophy; therefore, TR3 is a potential target for clinical therapy.<\/jats:p>","DOI":"10.1002\/emmm.201201369","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T13:08:15Z","timestamp":1354194495000},"page":"137-148","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The orphan receptor TR3 participates in angiotensin II\u2010induced cardiac hypertrophy by controlling mTOR signalling"],"prefix":"10.1038","volume":"5","author":[{"given":"Rong\u2010Hao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Ping","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao\u2010Long","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Dan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang\u2010Zi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Jia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi\u2010Xing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Xiu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong\u2010Gui","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahuai","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chawnshang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,11,29]]},"reference":[{"key":"BFEMMM201201369_CR1","doi-asserted-by":"crossref","first-page":"H2905","DOI":"10.1152\/ajpheart.00323.2006","volume":"291","author":"DD Belke","year":"2006","unstructured":"Belke DD, Gloss B, Hollander JM, Swanson EA, Duplain H, Dillmann WH (2006) In vivo gene delivery of HSP70i by adenovirus and adeno\u2010associated virus preserves contractile function in mouse heart following ischemia\u2010reperfusion. 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