| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Outline of Final Research Achievements |
We investigated factors stimulating differentiation of skeletal muscle satellite cells (SMSCs), and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes effects of hypoxia on preferential self-renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to tricarboxylic acid (TCA) cycle by producing acetyl coA from pyruvate. PDH kinase 1 is decreased under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation skeletal muscle regeneration upon injury, and aggravated pathogenesis of dystrophin-deficient mice. Thus, the metabolic flow from glycolysis to TCA cycle mediated by PDH plays a pivotal role in the efficient differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.
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