| Project/Area Number |
17208024
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied animal science
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAGUCHI Takahiro Tohoku University, Tohoku University, Graduate School of Agricultural Science, Professor (20111297)
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| Co-Investigator(Kenkyū-buntansha) |
ASO Hisashi Tohoku University, Graduate School of Agricultural Science, Assistant Professor (50241625)
WATANABE Kouichi Tohoku University, Graduate School of Agricultural Science, Assistant Professor (80261494)
HASEGAWA Yoshihisa Kitasato University, School of Veterinary Medicine, Professor (40092001)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2007: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Fiscal Year 2006: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2005: ¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
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| Keywords | Myostatin / Bovine skeletal muscle / Double-muscled cattle / Muscular growth and differentiation factors / Muscular transcription factors / myoblasts / Endocrine effect / ウシ骨格筋 / ミオスタチンレセプター / 骨格筋成長因子 / 骨格筋の転写因子 / ウシ筋肉内脂肪前駆細胞 |
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| Research Abstract |
The present study was conducted to analyze the entire mechanisms that double muscled phenotype of Japanese shorthorn cattle (spontaneous myostatin-deficient cattle: DM cattle) induces the increased muscle mass. The research for three years form 2005 to 2007 resulted in several new information as follows.
1) In the myoblast (DM myoblast) cultures derived from the M. longissimus thoracis of DM cattle, myostatin suppressed the expression of IGF-2 but not IGF-1, and HGF and aFGF that stimulate myoblast proliferation augmented the myostatin expression. But myostatin did not influence the HGF expression. These findings indicate that the increased muscle mass in DM cattle largely depends on deficient myostatin production by HGF produced in myoblasts.
2) By microarray analysis, it was defined that the expression of TGF-β inducible early gene family 2 (TIEG-2) that is associated with myostatin intracellular signal pathway was 4.5 times more in DM cattle than control cattle. Knockdown of TIEG-1 by
… More
siRNA led the increased cell growth and myotube formation, and further the enhanced expression of number of MyoD family, MRF4 and IGF-2. These findings indicate that TIEG-1 is closely associated with myostatin intracellular signaling as one of specific factors.
3) Nine kinds of cloned DM myoblast cell line (DMc) were first established from DM myoblasts and then the inmortal cloned DM myoblast cell line (DMc-t) was produced from DMc. These cell lines are very convenient to precisely understand myostatin action on muscle differentiation and growth.
4) Myostatin was similarly detected in the muscle of IGF-1 knockout and wild type mice. IGF-2 expression was stronger in the M. longissimus thoracis of DM cattle than control cattle than control cattle. Myostatin suppressed IGF-2 expession and was no effect on IGF-1 expression in DMc cultures. But the expression of activin receptor type IIB (ActRIIB) to be myostatin receptor and IGF-1 receptor was not influenced by myostatin The results show that myostatin and IGF-2 reciprocally act and myostatin and IGF-1 independently act on muscle differentiation and regeneration of muscle.
5) Immunohistochemistry revealed that myostatin was mainly contained in thyrotrophs and ActRIIB was detected in corticotrophs in the adenohypophysis of cattle and pigs. A lot of thyrotrophs positive for myostatin was located adjacently the corticotrophs positive for ActRIIB. The findings show that myostatin released from thyrotrophs acts on corticotrophs by paracrine pathway.
6) Mouse ACTH adenoma cell line, AtT-20 cells were expressed ActRIIB. By myostatin addition to the AtT-20 cell cultures, the POMC expression and ACTH immunoreactivity in the cells were substantially suppressed. The results first show that MSTN directly suppresses the ACTH production in ACTH cells.
The present study was proceeded according to schedules and obtained the results available to fully understand myostain action on muscle differentiation and growth. Less
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