These authors contributed equally to this work.
The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signalling
Article first published online: 29 NOV 2012
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 1, pages 137–148, January 2013
How to Cite
Wang, R.-H., He, J.-P., Su, M.-L., Luo, J., Xu, M., Du, X.-D., Chen, H.-Z., Wang, W.-J., Wang, Y., Zhang, N., Zhao, B.-X., Zhao, W.-X., Shan, Z.-G., Han, J., Chang, C. and Wu, Q. (2013), The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signalling. EMBO Mol Med, 5: 137–148. doi: 10.1002/emmm.201201369
- Issue published online: 3 JAN 2013
- Article first published online: 29 NOV 2012
- Manuscript Accepted: 10 OCT 2012
- Manuscript Revised: 8 OCT 2012
- Manuscript Received: 13 MAR 2012
- Funded Access
- angiotensin II;
- cardiac hypertrophy;
- mammalian target of rapamycin;
- orphan receptor TR3;
- tuberous sclerosis complex
Angiotensin II (AngII) induces cardiac hypertrophy and increases the expression of TR3. 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-induced cardiac hypertrophy compared with the respective controls. A mechanistic analysis demonstrates that the TR3-mediated activation of mTORC1 is associated with AngII-induced 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.