詳細ページ（後藤勝正）
氏名
後藤 勝正
職位
教授
連絡先
E-mail：goto@sozo.ac.jp
表題
骨格筋の可塑性制御機構
主な研究と特徴
生体は種々の刺激（ストレス）を受容し、それに応答・適応して生きている。さらに、発育・発達・成熟・老化や様々な疾病・疾患により生体の機能は大きく変容を示す。その典型的な形の1つが生命の進化であると考えている。しかし、生体機能と一口で言っても、その機能は多種多様であり、アプローチ方法も様々である。
動物であるヒトは、地球上において重力環境下で生活している。そしてこの生活のために欠かせないのが、運動機能の中心的な役割を担う骨格筋である。そこで本研究室では、骨格筋機能に関連する様々な生体機能とそれらに影響を与える因子を探求すると共に、生活の質（Quality of Life：QOL）や健康を維持増進していくために必要な生体応答に関する総合的な課題についての研究を展開している。現在実施している研究テーマとしては「骨格筋の可塑性制御機構」「骨格筋再生機構」「サルコペニア・ロコモティシンドロームの分子機構解明とその対策」「骨格筋組織内脂肪量の調節」「筋生理学」「宇宙医学」「人体生理学」になる。
「骨格筋可塑性制御機構」に関する研究では、骨格筋の持つ大きな可塑性、すなわち良く使うことで肥大し、不使用などにより萎縮するという性質の制御機構を解明するべく、骨格筋組織幹細胞である筋衛星細胞（筋サテライトセル）の機能解析を中心に検討を行っている。この筋衛星細胞は、損傷した骨格筋組織の再生において中心的な役割を担っており、「骨格筋再生機構」の研究と関連している。骨格筋の萎縮と脆弱化は加齢によってももたらされる。これを加齢性筋肉減弱症（サルコペニア）と呼ぶ。サルコペニアはヒトの運動機能を著しく減退させる。こうした状況は、ロコモティブシンドロームと呼び、QOL低下の主要因の1つである。したがって、骨格筋量と張力の維持・向上を目指す、骨格筋可塑性制御機構の解明の意義は大きい。さらに、骨格筋の可塑性を修飾する因子としては荷重負荷を挙げることができるが、この荷重負荷は1 gという重力環境でもたらされるものであり、重力が極めて小さくなる宇宙空間では骨格筋は萎縮してしまう。国際宇宙ステーションをはじめ宇宙開発が国策として推進されているが、宇宙環境に曝露された際の骨格筋の適応変化とそれに対するカウンターメジャーの開発もまた主要な研究テーマの1つである。
また、骨格筋は人体最大の糖脂質代謝器官である。したがって、生活習慣病などの基盤となるメタボリックシンドロームの予防と改善には骨格筋機能の維持向上が鍵となると考えている。最近、当研究室では骨格筋細胞に発現するアディポカインの1つであるadiponectinが、骨格筋量の変化に伴って変動することを見出した。アディポカインはその名の通り脂肪細胞が産生し分泌すると一般的に考えられているが、骨格筋細胞でのadiponectin発現量の変動が全身糖脂質代謝の調節において重要な役割を担っていると考え検討を行っている。
主な研究手法としては、実験動物（野生型ならびに遺伝子組み換えマウス）および培養細胞を対象として、遺伝子発現ならびにタンパク質の発現についてウェスタンブロッティング法ならびに定量real time-RT PCR法などを駆使して検討を行っている。こうした研究の多くは、国内外の研究者との共同研究として実施されている
今後の展望
骨格筋機能はヒトが健康な生活を営む上で必須であり、その機能だけでなく筋肉量の維持向上も重要であることは言うまでもない。骨格筋量ならびに機能の制御機構を明らかにすることで、健康長寿社会に貢献していきたいと考えている。
経歴
平成3年聖マリアンナ医科大学第二生理学教室助手
平成10年医学博士
平成11年聖マリアンナ医科大学生理学教室講師、同大学院医学研究科講師
平成16年豊橋創造大学リハビリテーション学部教授
平成21年豊橋創造大学保健医療学部教授
平成22年豊橋創造大学大学院健康科学研究科研究科長・教授
令和4年豊橋創造大学副学長。豊橋創造大学短期大学部副学長。
その他、聖マリアンナ医科大学客員教授、弘前学院大学客員教授、他。
所属学会
日本生理学会評議員、日本体力医学会理事・評議員、日本宇宙航空環境医学会理事長代行・理事・評議員、日本運動生理学会評議員、American Physiological Society、American Society for Gravitational and Space Research、International Society for Gravitational Physiology、他。
Editor-in-Chief of Journal of Physical Fitness and Sports Medicine、体力科学編集委員長、The Editorial Board Member of the Journal of Physiological Sciences、日本体力医学会編集委員会編集委員長、日本宇宙航空環境医学会編集委員、他。
主要論文・著書
【主要論文】
1. Activation of lactate receptor positively regulates skeletal muscle mass in mice. Physiol. Res., 72: 465-473, 2023.
2. Impacts of myosin heavy chain phenotypes on recovery of leg extension force after ACL-reconstructed knee. J. Phys. Fitness Sports Med. 12: 77-85, 2023.
3. Skeletal muscle denervation: sciatic and tibial nerve transection technique. Methods Mol. Biol. Vol. 2460: 217-225, 2023.
4. Responses of neuromuscular properties to unloading and potential countermeasures during space exploration missions. Neurosci. Biobehav. Rev. 136: 104617, 2022.
5. Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle. J. Appl. Physiol. 132: 477-488, 2022.
6. Fine-tuning of Piezo1 expression and activity ensures efficient myoblast fusion during skeletal myogenesis. Cells 11: 393, 2022.
7. Role(s) of gravitational loading on the growth and development of neuromuscular properties. Aerosp. Environ. Med. 54: 73-79, 2020.
8. MBNL1-associated mitochondrial dysfunction and apoptosis in C2C12 myotubes and mouse skeletal muscle. Int. J. Mol. Sci. 21: 6376, 2020.
9. Involvement of receptor for advanced glycation end products in microgravity-induced skeletal muscle atrophy in mice. Acta Astronaut. 176: 332-340, 2020.
10. Roles of satellite cells and/or myonuclei in the regeneration of morphological properties of anti-gravitational skeletal muscle in response to mechanical stress. Biol. Sci. Space 34: 1-11, 2020.
11. Role of active plantar-flexion and/or passive dorsi-flexion of ankle joints as the countermeasure for unloading-related effects in human soleus. Acta Astronaut. 175: 174-178, 2020.
12. Role of 72-kDa heat shock protein in heat-stimulated regeneration of injured muscle in rat. J. Histochem. Cytochem., 64: 791-799, 2019.
13. The protective effect of Brazilian propolis against glycation stress in mouse skeletal muscle. Foods, 8: 439, 2019.
14. Impact of different temperature stimuli on the expression of myosin heavy chain isoforms during recovery from bupivacaine-induced muscle injury in rats. J. Appl. Physiol., 127: 178-189, 2019.
15. MENS-associated increase of muscular protein content via modulation of caveolin-3 and TRIM72. Physiol. Res., 68: 255-264, 2019.
16. Lactate stimulates a potential for hypertrophy and regeneration of mouse skeletal muscle. Nutrients, 11, 869, 2019.
17. Nuclear accumulation of HSP70 in mouse skeletal muscles in response to heat stress, aging, and unloading with or without reloading. Front. Genet., 9: 617, 2018.
18. Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy. J. Zhejiang Univ. Sci. B, 19: 844-852, 2018.
19. Activation of adiponectin receptors has negative impact on muscle mass in C2C12 myotubes and fast-type mouse skeletal muscle. PLoS ONE, 13: e0205645, 2018.
20. AMPK mediates muscle mass change but not the transition of myosin heavy chain isoforms during unloading and reloading of skeletal muscles in mice. Int. J. Mol. Sci., 19: 2954, 2018.
21. The effect of advanced glycation end products on cellular signaling molecules in skeletal muscle. J. Phys. Fitness Sports Sci., 7: 229-238, 2018.
22. Age-related changes in myostatin expression in rat skeletal muscles. J. Phys. Fitness Sports Sci., 7: 221-227, 2018.
23. Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12 cells. Acta Physiol., 223: e13042, 2018.
24. Detrimental responses of the properties in rat soleus muscle to passive continuous stretch. Jpn J Aerospace Environ Med, 54: 37-44, 2017.
25. Long term changes in muscles around the knee joint after ACL resection in rats: Comparisons of ACL-resected, contralateral and normal limb. J. Sports Sci. Med., 16: 429-437, 2017.
26. Effects of palatinose-containing diet with exercise on progression of diabetic nephropathy and metabolic syndorome in obese-diabetic rats. Eur. J. Sports Exerc. Sci., 5: 26-36, 2017.
27. Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice. Br. J. Nutr., 117: 21-29, 2017.
28. Dietary astaxanthin supplementation attenuates disuse-induced muscle atrophy and myonuclear apoptosis in the rat soleus muscle. J. Physiol. Sci., 67: 181-190, 2016.
29. Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats. Physiol. Rep., 4: e12885, 2016.
30. Suppression of myostatin stimulates regenerative potential of injured antigravitational soleus muscle in mice under unloading condition. Int. J. Med. Sci., 13: 680-685, 2016.
31. Heat shock transcription factor 1-associated expression of slow myosin heavy chain in mouse soleus muscle in response to unloading with or without reloading. Acta Physiol., 217: 325-337, 2016.
32. Caffeine affects myotube size as well as regulates protein degradation and protein synthesis pathways in C2C12 skeletal muscle cells. J. Caffeine Res., 6: 88-96, 2016.
33. News aspect of microcurrent electrical muscular stimulation in sports medicine. J. Phys. Fitness Sports Med., 5: 69-72, 2016.
34. Heat stress acutely activates insulin-independent glucose transport and 5'-AMP-activated protein kinase prior to an increase in HSP72 in rat skeletal muscle. Physiol. Rep., 3: e12601, 2015.
35. Regeneration of injured tibialis anterior muscle in mice in response to microcurrent electrical neuromuscular stimulation with or without icing. J. St. Marianna Univ., 6: 159-169, 2015.
36. Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice. Acta Physiol., 215: 191-203, 2015.
37. Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice．Am. J. Physiol. Endocrinol. Metab., 309: E651-E662, 2015.
38. Responses of skeletal muscles to gravitational unloading and/or reloading. J. Physiol. Sci. 65: 293-310, 2015.
39. Microcurrent electrical stimulation facilitates regeneration of injured skeletal muscle in mice. J. Sports Sci. Med. 14: 297-303, 2015.
40. Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents muscle hypertrophy in single soleus fibers. Am. J. Physiol. Cell Physiol. 308: C848-C855, 2015.
41. Loading-associated expression of TRIM72 and caveorin-3 in antigravitational soleus muscle in mice. Physiol. Rep. 2: e12259, 2014.
42. Effects of catechin-ingestion and heat stress on the maximum isometric force in knee extension, the volume of quadriceps muscle, and serum thiobarbituric acid reactive substances level in healthy elderly women. J. Gerontol. Geriat. Res. 3: 148, 2014.
43. Activation of 5’AMP-activated protein kinase in skeletal muscle by exercise and phytochemicals. J. Phys. Fitness Sports Med. 3: 55-64, 2014.
44. AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through HSP72-mediated pathway in C2C12 skeletal muscle cells. Am. J. Physiol. Endocrinol. Metab. 306: E344-E354, 2014.
45. Effects of gravitational loading levels on protein expression related to metabolic and/or morphologic properties of mouse neck muscles. Physiol. Rep. 2: e00183, 2014.
46. Icing at early stage depresses skeletal muscle regeneration. J. St. Marianna Univ. 4: 61-67, 2013.
47. Effects of STG tendon harvest and BTB harvest on knee joint muscles -An immunohistochemical evaluation-. J. St. Marianna Univ. 4: 49-59, 2013.
48. Up-regulation of adiponectin expression in antigravitational soleus muscle in response to unloading followed by reloading, and functional overloading in mice. PLoS ONE 8: e81929, 2013.
49. Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle. PLoS ONE 8: e77788, 2013.
50. Regeneration of injured skeletal muscle in heat shock transcription factor 1-null mice. Physiol. Rep. 1: e00071, 2013.
51. Microcurrent electrical nerve stimulation facilitates regrowth of mouse soleus muscle. Intl. J. Med. Sci. 10: 1286-1294, 2013.
52. Increased dystrophin mRNA and protein levels in atrophic skeletal muscles in streptozotocin-induced diabetic rat. J. Phys. Fit. Sports Med., 1: 709-713, 2012.
53. Effects of heat stress on muscle mass and the expression levels of heat shock proteins and lysosomal cathepsin L in soleus muscle of young and aged mice. Mol Cell Biochem, 369: 45-53, 2012.
54. Some aspects of heat stress on the plasticity of skeletal muscle cells. J. Phys. Fit. Sports Med. 1: 197-204, 2012.
55. Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days. PLoS ONE 7: e40112, 2012.
56. The impact of long-term exposure to space environment on adult mammalian organisms: A study on mouse thyroid and testis. PLoS ONE 7: e35418, 2012.
57. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission. PLoS ONE 7: e33232, 2012.
58. Absence of heat shock transcription factor 1 retards the regrowth of atrophied soleus muscle in mice. J. Appl. Physiol.,111: 1142-1149, 2011.
59. Responses of muscle mass, strength and gene transcripts to long-term heat stress in healthy human subjects. Eur. J. Appl. Physiol., 111: 17-27, 2011.
60. Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers. J. Appl. Physiol., 108: 676-685, 2010.
61. Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in mice. Acta Physiol., 196: 329-339, 2009.
62. Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3ab signals. Eur. J. Appl. Physiol., 105: 643-651, 2009.
63. Functional overloading facilitates the regeneration of injured soleus muscles in mice. J. Physiol. Sci., 58: 397-404, 2008.
64. Geranylgeranylaceton induces heat shock protein 72 in skeletal muscles. Biochem. Biophys. Res. Commun., 358: 331-335, 2007.
65. Skeletal muscle hypertrophy induced by low-intensity exercise with heat-stress in healthy human subjects. Jpn. J. Aerospace Environ. Med., 44: 13-18, 2007.
66. Possible role of calcineurin in heating-related increase of rat muscle mass. Biochem. Biophys. Res. Commun., 331: 1301-1309, 2005.
67. Changes in protein kinase B (PKB/Akt) and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading. Am. J. Physiol. Regul. Integr. Comp. Physiol., 288: R1273-R1278, 2005.
68. Effects of heat stress and mechanical stretch on protein expression in cultured skeletal muscle cells. Pfügers Arch., 447: 247-253, 2003.
69. Profiles of connectin (titin) in atrophied soleus muscle induced by unloading rats. J. Appl. Physiol., 94: 897-902, 2003.
【著書】
1. Egawa, T., Kido, K., Yokokawa, T., Fujibayashi, M., Goto, K., Hayashi, T.: The effect of glycation stress in skeletal muscle. In: Psychology and Patho-physiological Outcomes of Eating, Takada, A. (ed.), IntechOpen, Rijeka, 2021. doi: 10.5772/intechopen.97769
2. Egawa, T., Tsuda, S., Oshima, R., Goto, A., Ma, X., Goto, K., and Hayashi, T.: Regulatory mechanism of skeletal muscle glucose transport by phenolic acids. In: Phenolic Compounds – Biological Activity, Soto-Hernández, M. (ed.), p. 169-191, In Tech, Rijeka, 2017.
3. Ortuste Quiroga, H.P., Goto, K., and Zammit, P.S.: Isolation, Cryosection and Immunostaining of skeletal muscle. In: Methods in Molecular Biology “Skeletal Muscle Regeneration in the Mouse” (Vol. 1460), Kyba, M. (ed.), p. 85-100, Springer (Springer-Verlag New York Inc.), New York, 2016.
4. Egawa, T., Tsuda, S., Hamada, T., Goto, K., and Hayashi, T.: Regulation mechanism of caffeine on glucose transport and upstream signaling pathways in skeletal muscle. In: Caffeine: Consumption, Side Effects and Impact on Performance and Mood, Tolley, AS. (ed.), p. 113-138, Nova Science Publishers, New York, 2014.
5. Goto, K., Ohira, Y., and Yoshioka, T.: Heat stress: A hypertrophic stimulus for skeletal muscles. In: Muscle Cell Physiology, Ohira, Y. (ed), p. 41-50, Osaka University Press, Osaka, 2009.
