| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Outline of Final Research Achievements |
We have found that dietary provitamin A β-carotene increased soleus muscle mass with hypertrophy by activating the retinoic acid receptor (RAR) γ in mice. In myotube cells, ATRA increased transglutaminase 2 (TG2) expression in an RARγ-dependent manner and TG2 was secreted into extracellular space. The expression of TG2 was also increased in an RARγ-dependent manner in the soleus muscle of β-carotene-fed mice. Extracellular TG2 activated mTOR signaling pathway through GPR56, promoted protein synthesis, and induced hypertrophy of myotubes. TG2 mutant lacking TG activity exerted the same effects as wild-type TG2. Intraperitoneally administration of TG2 increased soleus muscle mass in mice. These results indicated that TG2 expression was upregulated through ATRA-mediated RARγ and that extracellular TG2 induced myotube hypertrophy by activating mTOR signaling-mediated protein synthesis through GPR56, independent of transglutaminase activity.
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