The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signalling.
Bottom Line: 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.The elimination or reduction of TR3 may reduce cardiac hypertrophy; therefore, TR3 is a potential target for clinical therapy.
Affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China.Show MeSH
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Mentions: A recent study demonstrated increased TR3 expression in the transverse aorta constriction (TAC) mouse model, which can induce pathological cardiac hypertrophy (Cheng et al, 2011). Similar to TAC, AngII has been reported to cause pathological cardiac hypertrophy. Therefore, we investigated whether TR3 is involved in AngII-induced cardiac hypertrophy. To establish a model of AngII-induced cardiac hypertrophy, 12-week-old WT mice and age-matched TR3-knockout (TR3-KO) littermates were implanted with osmotic minipumps to administer AngII continuously for 4 weeks. TR3 expression in the WT mice and the BP of mice with both genotypes were upregulated within 4 weeks. However, the increase in BP by AngII was comparable between the WT and TR3-KO mice (Fig 1A and Supporting Information Fig S1A). These results suggest that TR3 expression, rather than BP, may cause the difference in phenotype between the WT and TR3-KO mice.
Affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China.