오르막-내리막 운동형태에 따른 노화쥐 골격근 내 Wnt/BMP 신호전달이 골격근 형성기전에 미치는 영향
The Effect of Uphill and Downhill Exercise Training on Myogenic Mechanism of Wnt/BMP Signaling in the Skeletal Muscle of Aged Rats
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
PURPOSE: The purpose of this study was to determine the effect of exercise types on the Wnt/BMP signaling and the response to myogenic mechanism by downhill and uphill training in the aged rat skeletal muscles. METHODS: Young and old rats were randomly assigned to control groups; young (YC) and old (OC), and two types of running training groups: old downhill exercise (ODE) and old uphill exercise (OUE). Training was progressively carried out on a treadmill at a speed of 21 m/min with a slope of +10° for uphill training vs 16 m/min with a slope of -16° for downhill training: 60 min/day, 5 days/week for 8 weeks respectively. RESULTS: Downhill and uphill training significantly increased the protein levels of Wnt3a, β-catenin and LEF-1 in aged rats. On the contrary, GSK3β was reduced by running training. In addition, the expression patterns of Wnt7a, Fzd7, PKC, p-AKT, and p-mTOR in extensor digitorum longus (EDL) and soleus (SOL) muscle were significantly increased in both ODE and OUE groups. Expression patterns of BMP-2, BMP-7, and p-Smad-1/5/8 in EDL and SOL muscles were significantly increased in both ODE and OUE groups. Especially, ODE group showed more increased expression pattern than OUE group. The expression patterns of MyoD, Myf5, and Myogenin were significantly increased in both DOE and OUE groups. Myf5 and Myogenin showed more increased expression pattern in ODE group than OUE group. CONCLUSIONS: The downhill and uphill exercise training may play a mediating role in increasing the expression of these reduced myogenesis related factors. Furthermore, the formation process and hypertrophy of skeletal muscle weakened due to aging can be improved and maintained.
Abstract
PURPOSE: The purpose of this study was to determine the effect of exercise types on the Wnt/BMP signaling and the response to myogenic mechanism by downhill and uphill training in the aged rat skeletal muscles. METHODS: Young and old rats were randomly assigned to control groups; young (YC) and old (OC), and two types of running training groups: old downhill exercise (ODE) and old uphill exercise (OUE). Training was progressively carried out on a treadmill at a speed of 21 m/min with a slope of +10° for uphill training vs 16 m/min with a slope of -16° for downhill training: 60 min/day, 5 days/week for 8 weeks respectively. RESULTS: Downhill and uphill training significantly increased the protein levels of Wnt3a, β-catenin and LEF-1 in aged rats. On the contrary, GSK3β was reduced by running training. In addition, the expression patterns of Wnt7a, Fzd7, PKC, p-AKT, and p-mTOR in extensor digitorum longus (EDL) and soleus (SOL) muscle were significantly increased in both ODE and OUE groups. Expression patterns of BMP-2, BMP-7, and p-Smad-1/5/8 in EDL and SOL muscles were significantly increased in both ODE and OUE groups. Especially, ODE group showed more increased expression pattern than OUE group. The expression patterns of MyoD, Myf5, and Myogenin were significantly increased in both DOE and OUE groups. Myf5 and Myogenin showed more increased expression pattern in ODE group than OUE group. CONCLUSIONS: The downhill and uphill exercise training may play a mediating role in increasing the expression of these reduced myogenesis related factors. Furthermore, the formation process and hypertrophy of skeletal muscle weakened due to aging can be improved and maintained.
참고문헌 (32)
- Kelleher AR, "STZ-induced skeletal muscle atrophy is associated with increased p65 content and downregulation of insulin pathway without NF-jB canonical cascade activation", Acta Diabetol, 47, pp.315~323 (2010)
- Taekema DG, "Circulating levels of IGF1 are associated with muscle strength in middle-aged-and oldest-old women", Eur J Endocrinol, 164, pp.189~196 (2011)
- Doherty TJ, "Invited review : aging and sarcopenia", J Appl Physiol, 95, pp.1717~1727 (2003)
- Amin H, "GSK3β inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running", J Physiol Sci, 64, pp.1~11 (2014)
- Kim JS, "Gradual downhill running improves age-related skeletal muscle and bone weakness: implication of autophagy and bone morphogenetic proteins", Exp Physiol, 101, pp.1528~1540 (2016)
- Simpson RJ, "Coupling aging immunity with a sedentary lifestyle : has the damage already been done?--a mini-review", Gerontology, 56, pp.449~458 (2010)
- Yoshihara D, "Antioxidants : benefits and risks for long-term health", Maturitas, 67, pp.103~107 (2010)
- Kim JS, "Intermittent bout exercise training down-regulates age-associated inflammation in skeletal muscles", Exp Gerontol, 72, pp.261~268 (2015)
- Lewis EJ, "Mild eccentric exercise increases Hsp72 content in skeletal muscles from adult and late middle-aged rats", Cell Stress Chaperones, 18, pp.667~673 (2013)
- Da Rocha AL, "Downhill running excessive training inhibits hypertrophy in mice skeletal muscles with different fiber type composition", J Cell Physiol, 231, pp.1045~1056 (2015)
- Kaux JF, "Eccentric training improves tendon biomechanical properties : a rat model", J Orthop Res, 31, pp.119~124 (2013)
- Tsivitse S, "Notch and Wnt signaling, physiological stimuli and postnatal myogenesis", Int J Biol Sci, 6, pp.268~281 (2010)
- Reya T, "Wnt signalling in stem cells and cancer", Nature, 434, pp.843~850 (2005)
- Moon RT, "WNT and beta-catenin signalling : diseases and therapies", Nat Rev Genet, 5, pp.691~701 (2004)
- Von Maltzahn J, "Wnt signaling in myogenesis", Trends Cell Biol, 22, pp.602~609 (2012)
- Von Maltzahn J, "Wnt7a-Fzd7 signalling directly activates the Akt", mTOR anabolic growth pathway in skeletal muscle, 2011, pp.14, 186~191
- Brack A, "A temporal switch from Notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis", Cell Stem Cell, 2, pp.50~59 (2008)
- Brack AS, "Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis", Science, 317, pp.807~810 (2007)
- Gazzerro E, "Bone morphogenetic proteins and their antagonists", Rev Endocr Metab Disord, 7, pp.51~65 (2006)
- Sartori R, "BMP signaling controls muscle mass", Nat Genet, 45, pp.1309~1318 (2013)
- Winbanks CE, "The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass", J Cell Biol, 203, pp.345~357 (2013)
- Perez VA, "BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways", J Cell Biol, 192, pp.171~188 (2011)
- Luo L, "Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt", mTOR and Akt, Exp Gerontol, pp.2013, 48[DOI]
- Hanna MA, "Structural remodeling of coronary resistance arteries : effects of age and exercise training", J Appl Physiol, 117, pp.616~623 (2014)
- Pasini E, "Effects of treadmill exercise and training frequency on anabolic signaling pathways in the skeletal muscle of aged rats", Exp Gerontol, 47, pp.23~28 (2012)
- Masiero E, "Autophagy is required to maintain muscle mass", Cell Metab, 10, pp.507~515 (2009)
- Lollo PC, "Differential response of heat shock proteins to uphill and downhill exercise in heart, skeletal muscle, lung and kidney tissues", J Sports Sci Med, 12, pp.461~466 (2013)
- Liu F, "Wnt signaling and skeletal development", Cell signal, 20, pp.999~1009 (2008)
- MacDonald BT, "Wnt", beta-catenin signaling : components, mechanisms, and diseases, 2009, pp.17, 9~26
- Matsakas A, "Intracellular signalling pathways regulating the adaptation of skeletal muscle to exercise and nutritional changes", Histol Histopathol, 24, pp.209~222 (2009)
- Matsumoto Y, "Estrogen and glucocorticoid regulate osteoblast differentiation through the interaction of bone morphogenetic protein-2 and tumor necrosis factor-alpha in C2C12 cells", Mol Cell Endocrinol, 325, pp.118~127 (2010)
- Sartori R, "TGFβ and BMP signaling in skeletal muscle : potential significance for muscle-related disease", Trends Endocrinol Metab, 25, pp.464~471 (2014)