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The Journal of Physiological Sciences

, Volume 64, Issue 1, pp 1–11 | Cite as

GSK3β inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running

  • Hiral Amin
  • Judy Vachris
  • Alicia Hamilton
  • Nury Steuerwald
  • Reuben Howden
  • Susan Tsivitse ArthurEmail author
Original Paper

Abstract

Canonical Wnt signaling is important in skeletal muscle repair but has not been well characterized in response to physiological stimuli. The objective of this study was to assess the effect of downhill running (DHR) on components of Wnt signaling. Young, male C57BL/J6 mice were exposed to DHR. Muscle injury and repair (MCadherin) were measured in soleus. Gene and protein expression of Wnt3a, active β-catenin, GSK3β, and LEF1 were measured in gastrocnemius. Muscle injury increased 6 days post-DHR and MCadherin protein increased 5 days post-DHR. Total and active GSK3β protein decreased 3 days (9-fold and 3.6-fold, respectively) post-DHR. LEF1 protein increased 6 days (5-fold) post-DHR. DHR decreased GSK3β and increased LEF1 protein expression, but did not affect other components of Wnt signaling. Due to their applicability, using models of physiological stimuli such as DHR will provide significant insight into cellular mechanisms within muscle.

Keywords

DHR Skeletal muscle repair Wnt Exercise 

Notes

Acknowledgment

We thank Dr. S. Peter Magnusson for insightful feedback and discussion on the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Karalaki M, Fili S, Philippou A, Koutsilieris M (2009) Muscle regeneration: cellular and molecular events. In Vivo 23:779–796PubMedGoogle Scholar
  2. 2.
    Charge S, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238PubMedCrossRefGoogle Scholar
  3. 3.
    Polesskaya A, Seale P, Rudnicki MA (2003) Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell 113:841–852PubMedCrossRefGoogle Scholar
  4. 4.
    Brack A, Conboy IM, Conboy MJ, Shen J, Rando TA (2008) A temporal switch from Notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis. Cell Stem Cell 2:50–59PubMedCrossRefGoogle Scholar
  5. 5.
    Brack A, Murphy-Seiler F, Hanifi J, Deka J, Eyckerman S, Keller C, Aguet M, Rando TA (2009) BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Dev Biol 335:93–105PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Tsivitse S (2010) Notch and Wnt signaling, physiological stimuli and postnatal myogenesis. Int J Biol Sci 6:268–281PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Ridgeway A, Petropoulos H, Wilton S, Skerjanc IS (2000) Wnt signaling regulates the function of MyoD and myogenin. J Biol Chem 275:32398–32405PubMedCrossRefGoogle Scholar
  8. 8.
    Cossu G, Borello U (1999) Wnt signaling and the activation of myogenesis in mammals. EMBO J 18:6867–6872PubMedCrossRefGoogle Scholar
  9. 9.
    Arce L, Yokoyama NN, Waterman ML (2006) Diversity of LEF/TCF action in development and disease. Oncogene 25:7492–7504PubMedCrossRefGoogle Scholar
  10. 10.
    Nusse R (2005) Wnt signaling in disease and in development. Cell Res 15:28–32PubMedCrossRefGoogle Scholar
  11. 11.
    van der Velden J, Langen RC, Kelders MC, Wouters EF, Janssen-Heininger YM, Schols AM (2006) Inhibition of glycogen synthase kinase-3beta activity is sufficient to stimulate myogenic differentiation. Am J Physiol Cell Physiol 290:C453–C462PubMedCrossRefGoogle Scholar
  12. 12.
    Otto A, Schmidt C, Luke G, Allen S, Valasek P, Muntoni F, Lawrence-Watt D, Patel K (2008) Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration. J Cell Sci 121:2939–2950PubMedCrossRefGoogle Scholar
  13. 13.
    Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J, Holcombe RF, Waterman ML (2001) Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet 28:53–57PubMedGoogle Scholar
  14. 14.
    Kengaku M, Capdevila J, Rodriguez-Esteban C, De La Pena J, Johnson RL, Izpisua Belmonte JC, Tabin CJ (1998) Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud. Science 280:1274–1277PubMedCrossRefGoogle Scholar
  15. 15.
    Ikeya M, Takada S (1998) Wnt signaling from the dorsal neural tube is required for the formation of the medial dermomyotome. Development 125:4969–4976PubMedGoogle Scholar
  16. 16.
    Sakanaka C, Sun TQ, Williams LT (2000) New steps in the Wnt/beta-catenin signal transduction pathway. Recent Prog Horm Res 55:225–236PubMedGoogle Scholar
  17. 17.
    Knight JD, Kothary R (2011) The myogenic kinome: protein kinases critical to mammalian skeletal myogenesis. Skelet Muscle 1:29PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Tanaka S, Terada K, Nohno T (2011) Canonical Wnt signaling is involved in switching from cell proliferation to myogenic differentiation of mouse myoblast cells. J Mol Signal 6:12PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Tsivitse S, Peters MG, Stoy AL, Mundy JA, Bowen RS (2009) The effect of downhill running on Notch signaling in regenerating skeletal muscle. Eur J Appl Physiol 106:759–767PubMedCrossRefGoogle Scholar
  20. 20.
    Smith H, Plyley MJ, Rodgers CD, McKee NH (1999) Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury. Eur J Physiol Occup Physiol 80:84–91CrossRefGoogle Scholar
  21. 21.
    Armand A, Launay T, Gapera BD, Charbonnier F, Gallien CL, Chanoine C (2003) Effects of eccentric treadmill running on mouse soleus: degeneration/regeneration studied with Myf-5 and MyoD probes. Acta Physiol Scand 179:75–84PubMedCrossRefGoogle Scholar
  22. 22.
    Tiidus P, Deller M, Liu XL (2005) Oestrogen influence on myogenic satellite cells following downhill running in male rats: a preliminary study. Acta Physiol Scand 184:67–72PubMedCrossRefGoogle Scholar
  23. 23.
    Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nature reviews. Endocrinology 8:457–465PubMedGoogle Scholar
  24. 24.
    Boppart M, Burkin DJ, Kaufman SJ (2006) Alpha7-Beta1-integrin regulates mechanotransduction and prevents skeletal muscle injury. Am J Physiol Cell Physiol 290:C1660–C1665PubMedCrossRefGoogle Scholar
  25. 25.
    Tsivitse S, McLoughlin TJ, Peterson JM, Mylona E, McGregor SJ, Pizza FX (2003) Downhill running in rats: influence on neutrophils, macrophages, and MyoD+ cells in skeletal muscle. Eur J Physiol Occup Physiol 90:633–638CrossRefGoogle Scholar
  26. 26.
    Jemiolo B, Trappe S (2004) Single muscle fiber gene expression in human skeletal muscle: validation of internal control with exercise. Biochem Biophys Res Commun 320:1043–1050PubMedCrossRefGoogle Scholar
  27. 27.
    von Maltzahn J, Chang NC, Bentzinger CF, Rudnicki MA (2012) Wnt signaling in myogenesis. Trends Cell Biol 22:602–609CrossRefGoogle Scholar
  28. 28.
    Armstrong D, Esser KA (2005) Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Am J Physiol Cell Physiol 289:C853–C859PubMedCrossRefGoogle Scholar
  29. 29.
    Ishido M, Uda M, Masuhara M, Kami K (2006) Alterations of M-cadherin, neural cell adhesion molecule and Beta-catenin expression in satellite cells during overload-induced skeletal muscle hypertrophy. Acta Physiol Scand 187:407–418Google Scholar
  30. 30.
    Arthur ST, Cooley ID (2012) The effect of physiological stimuli on sarcopenia; impact of Notch and Wnt signaling on impaired aged skeletal muscle repair. Int J Biol Sci 8:731–760PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Hardt SE, Sadoshima J (2002) Glycogen synthase kinase-3beta: a novel regulator of cardiac hypertrophy and development. Circ Res 90:1055–1063PubMedCrossRefGoogle Scholar
  32. 32.
    Hughes K, Nikolakaki E, Plyte SE, Totty NF, Woodgett JR (1993) Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J 12:803–808PubMedGoogle Scholar
  33. 33.
    Aschenbach W, Ho RC, Sakamoto K, Fujii N, Li Y, Kim YB, Hirshman MF, Goodyear LJ (2006) Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. Am J Physiol Endocrinol Metab 291:E152–E158PubMedCrossRefGoogle Scholar
  34. 34.
    Torii K, Nishizawa K, Kawasaki A, Yamashita Y, Katada M, Ito M, Nishimoto I, Terashita K, Aiso S, Matsuoka M (2008) Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways. Cell Signal 20:1256–1266PubMedCrossRefGoogle Scholar
  35. 35.
    Glass D (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37:1974–1984PubMedCrossRefGoogle Scholar
  36. 36.
    Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3:1009–1013PubMedCrossRefGoogle Scholar
  37. 37.
    Favier F, Benoit H, Freyssenet D (2008) Cellular and molecular events controlling skeletal muscle mass in response to altered use. Pflugers Arch 456:587–600PubMedCrossRefGoogle Scholar
  38. 38.
    Mayhew D, Kim JS, Cross JM, Ferrando AA, Bamman MM (2009) Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans. J Appl Physiol 107:1655–1662PubMedCrossRefGoogle Scholar
  39. 39.
    Kirwan J, del Aguila LF (2003) Insulin signalling, exercise and cellular integrity. Biochem Soc Trans 31:1281–1285PubMedCrossRefGoogle Scholar
  40. 40.
    Lueders TN, Zou K, Huntsman HD, Meador B, Mahmassani Z, Abel M, Valero MC, Huey KA, Boppart MD (2011) The alpha7beta1-integrin accelerates fiber hypertrophy and myogenesis following a single bout of eccentric exercise. Am J Physiol Cell Physiol 301:C938–C946PubMedCrossRefGoogle Scholar
  41. 41.
    Leal ML, Lamas L, Aoki MS, Ugrinowitsch C, Ramos MS, Tricoli V, Moriscot AS (2011) Effect of different resistance-training regimens on the WNT-signaling pathway. Eur J Appl Physiol 111:2535–2545PubMedCrossRefGoogle Scholar
  42. 42.
    Novak A, Dedhar S (1999) Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci: CMLS 56:523–537PubMedCrossRefGoogle Scholar
  43. 43.
    Labbe E, Letamendia A, Attisano L (2000) Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways. Proc Natl Acad Sci USA 97:8358–8363PubMedCrossRefGoogle Scholar
  44. 44.
    Luderer HF, Gori F, Demay MB (2011) Lymphoid enhancer-binding factor-1 (LEF1) interacts with the DNA-binding domain of the vitamin D receptor. J Biol Chem 286:18444–18451PubMedCrossRefGoogle Scholar
  45. 45.
    Riese J, Yu X, Munnerlyn A, Eresh S, Hsu SC, Grosschedl R, Bienz M (1997) LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell 88:777–787PubMedCrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2013

Authors and Affiliations

  • Hiral Amin
    • 2
  • Judy Vachris
    • 2
  • Alicia Hamilton
    • 2
  • Nury Steuerwald
    • 2
  • Reuben Howden
    • 1
  • Susan Tsivitse Arthur
    • 1
    Email author
  1. 1.Laboratory of Systems Physiology, Department of KinesiologyUNC CharlotteCharlotteUSA
  2. 2.Molecular Biology Core FacilityCannon Research CenterCharlotteUSA

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