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Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3αβ signals

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Abstract

Effects of administration of granulocyte colony-stimulating factor (G-CSF) on the regeneration of injured mammalian skeletal muscles were studied in male C57BL/6J mice. Muscle injury was induced by injection of cardiotoxin (CTX) into tibialis anterior muscles bilaterally. G-CSF was administrated for 8 consecutive days from 3 days before and 5 days after the injection. Significant decreases of wet weight and protein content were noted in the necrotic muscle with CTX injection. A large number of the regenerating fibers having central nucleus were observed 7 days after the injection. The regeneration of injured muscle was further facilitated by the G-CSF treatment. Population of Pax7-positive nuclei was increased by the G-CSF treatment at day 7. Phospho-Akt and phospho-glycogen synthase kinase 3αβ (GSK3αβ) signals were also activated by G-CSF-administrated group during the regenerative process. It was suggested that G-CSF treatment may facilitate the regeneration of injured skeletal muscles via the activation of Akt/GSK3αβ signals.

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References

  • Abedi M, Greer DA, Colvin GA, Demers DA, Dooner MS, Harpel JA, Weier HU, Lambert JF, Quesenberry PJ (2004) Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: a multifactorial process. Exp Hematol 32:426–434. doi:10.1016/j.exphem.2004.02.007

    Article  PubMed  CAS  Google Scholar 

  • Asakura A, Seale P, Girgis-Gabardo A, Rudnicki MA (2002) Myogenic specification of side population cells in skeletal muscle. J Cell Biol 159:123–134. doi:10.1083/jcb.200202092

    Article  PubMed  CAS  Google Scholar 

  • Barton-Davis ER, Shoturma DI, Musaro A, Rosenthal N, Sweeney HL (1998) Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci USA 95:15603–15607. doi:10.1073/pnas.95.26.15603

    Article  PubMed  CAS  Google Scholar 

  • Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 11:1014–1019. doi:10.1038/ncb1101-1014

    Article  CAS  Google Scholar 

  • Chargé SBP, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238. doi:10.1152/physrev.00019.2003

    Article  PubMed  Google Scholar 

  • Conejo R, Lorenzo M (2001) Insulin signaling leading to proliferation, survival, and membrane ruffling in C2C12 myoblasts. J Cell Physiol 187:96–108. doi:10.1002/1097-4652(2001)9999:9999<::AID-JCP1058>3.0.CO;2-V

    Google Scholar 

  • Couteaux R, Mira JC, d’Albis A (1998) Regeneration of muscles after cardiotoxin injury I. Cytological aspects. Biol Cell 62:171–182. doi:10.1016/0248-4900(88)90034-2

    Article  Google Scholar 

  • Dhawan J, Rando TA (2005) Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment. Trends Cell Biol 12:666–673. doi:10.1016/j.tcb.2005.10.007

    Article  CAS  Google Scholar 

  • Fang CH, Li BG, James JH, King JK, Evenson AR, Warden GD, Hasselgren PO (2005) Protein breakdown in muscle from burned rats is blocked by insulin-like growth factor 1 and glycogen synthase kinase-3β inhibitors. Endocrinology 146:3141–3149. doi:10.1210/en.2004-0869

    Article  PubMed  CAS  Google Scholar 

  • Fang CH, Li B, James JH, Yahya A, Kadeer N, Guo X, Xiao C, Supp DM, Kagan RJ, Hasselgren PO, Sheriff S (2007) GSK-3β activity is increased in skeletal muscle after burn injury in rats. Am J Physiol Regul Integr Comp Physiol 293:R1545–R1551. doi:10.1152/ajpregu.00244.2007

    PubMed  CAS  Google Scholar 

  • Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279:1528–1530. doi:10.1126/science.279.5356.1528

    Article  PubMed  CAS  Google Scholar 

  • Fletcher JE, Jiang MS (1993) Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. Toxicon 31:669–695. doi:10.1016/0041-0101(93)90375-S

    Article  PubMed  CAS  Google Scholar 

  • Goto K, Honda M, Kobayashi T, Uehara K, Kojima A, Akema T, Yamada S, Ohira Y, Yoshioka T (2004) Heat stress facilitates the recovery of atrophied soleus muscle in rat. Jpn J Physiol 54:285–293. doi:10.2170/jjphysiol.54.285

    Article  PubMed  CAS  Google Scholar 

  • Hawke TJ, Garry DJ (2001) Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 91:534–551

    PubMed  CAS  Google Scholar 

  • Iwanaga K, Takano H, Ohtsuka M, Hasegawa H, Zou Y, Qin Y, Odaka K, Hiroshima K, Tadokoro H, Komuro I (2004) Effects of G-CSF on cardiac remodeling after acute myocardial infarction in swine. Biochem Biophys Res Commun 325:1353–1359. doi:10.1016/j.bbrc.2004.10.149

    Article  PubMed  CAS  Google Scholar 

  • Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, Masaki H, Mori Y, Iba O, Tateishi E, Kosaki A, Shintani S, Murohara T, Imaizumi T, Iwasaka T (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 104:1046–1052. doi:10.1161/hc3501.093817

    Article  PubMed  CAS  Google Scholar 

  • Kojima A, Goto K, Morioka S, Naito T, Akema T, Fujiya H, Sugiura T, Ohira Y, Beppu M, Aoki H, Yoshioka T (2007) Heat stress facilitates the regeneration of injured skeletal muscle in rats. J Orthop Sci 12:74–82. doi:10.1007/s00776-006-1083-0

    Article  PubMed  Google Scholar 

  • Lawlor MA, Rotwein P (2000) Coordinate control of muscle cell survival by distinct insulin-like growth factor activated signaling pathways. J Cell Biol 151:1131–1140. doi:10.1083/jcb.151.6.1131

    Article  PubMed  CAS  Google Scholar 

  • Lockhart NC, Baar K, Mazzeo RS, Brooks SV (2006) Activation of Akt as a potential mediator of adaptations that reduce muscle injury. Med Sci Sports Exerc 38:1058–1064. doi:10.1249/01.mss.0000222832.43520.27

    Article  PubMed  CAS  Google Scholar 

  • Mauro A (1961) Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol 9:493–495

    Article  PubMed  CAS  Google Scholar 

  • Morgan JE, Partridge TA (2003) Muscle satellite cells. Int J Biochem Cell Biol 35:1151–1156. doi:10.1016/S1357-2725(03)00042-6

    Article  PubMed  CAS  Google Scholar 

  • Mourkioti F, Rosenthal N (2005) IGF-1, inflammation and stem cells: interactions during muscle regeneration. Trends Immunol 26:535–542. doi:10.1016/j.it.2005.08.002

    Article  PubMed  CAS  Google Scholar 

  • Musarò A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N (2001) Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet 27:195–200. doi:10.1038/84839

    Article  PubMed  Google Scholar 

  • Ohtsuka M, Takano H, Zou Y, Toko H, Akazawa H, Qin Y, Suzuki M, Hasegawa H, Nakaya H, Komuro I (2004) Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization. FASEB J 18:851–853

    PubMed  CAS  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001a) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705. doi:10.1038/35070587

    Article  PubMed  CAS  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001b) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98:10344–10349. doi:10.1073/pnas.181177898

    Article  PubMed  CAS  Google Scholar 

  • Reimann J, Brimah K, Schröder R, Wernig A, Beauchamp JR, Partridge TA (2004) Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures. Cell Tissue Res 315:233–242. doi:10.1007/s00441-003-0833-y

    Article  PubMed  Google Scholar 

  • Sartorelli V, Fulco M (2004) Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy. Sci STKE 244:11–27

    Google Scholar 

  • Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786. doi:10.1016/S0092-8674(00)00066-0

    Article  PubMed  CAS  Google Scholar 

  • Seale P, Asakura A, Rudnicki MA (2001) The potential of muscle stem cells. Dev Cell 1:333–342. doi:10.1016/S1534-5807(01)00049-1

    Article  PubMed  CAS  Google Scholar 

  • Stratos I, Rotter R, Eipel C, Mittlmeier T, Vollmar B (2007) Granulocyte-colony stimulating factor enhances muscle proliferation and strength following skeletal muscle injury in rats. J Appl Physiol 103:1857–1863. doi:10.1152/japplphysiol.00066.2007

    Article  PubMed  CAS  Google Scholar 

  • Takano H, Ohtsuka M, Akazawa H, Toko H, Harada M, Hasegawa H, Nagai T, Komuro I (2003) Pleiotropic effects of cytokines on acute myocardial infarction: G-CSF as a novel therapy for acute myocardial infarction. Curr Pharm Des 9:1121–1127. doi:10.2174/1381612033455008

    Article  PubMed  CAS  Google Scholar 

  • Uehara K, Goto K, Kobayashi T, Kojima A, Akema T, Sugiura T, Yamada S, Ohira Y, Yoshioka T, Aoki H (2004) Heat-stress enhances proliferative potential in rat soleus muscle. Jpn J Physiol 54:263–271. doi:10.2170/jjphysiol.54.263

    Article  PubMed  CAS  Google Scholar 

  • van der Velden JLJ, Langen RCJ, Kelders KCJM, Wouters EFM, Janssen-Heininger YMW, Schols AMWJ (2006) Inhibition of glycogen synthase kinase-3β activity is sufficient to stimulate myogenic differentiation. Am J Physiol Cell Physiol 290:C453–C462. doi:10.1152/ajpcell.00068.2005

    Article  PubMed  CAS  Google Scholar 

  • van der Velden JLJ, Langen RCJ, Kelders MCJM, Willems J, Wouters EFM, Janssen-Heininger YMW, Schols AMWJ (2007) Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3β. Am J Physiol Cell Physiol 292:C1636–C1644. doi:10.1152/ajpcell.00504.2006

    Article  PubMed  CAS  Google Scholar 

  • Vierck J, O’Reilly B, Hossner K, Antonio J, Byrne K, Bucci L, Dodson M (2000) Satellite cell regulation following myotrauma caused by resistance exercise. Cell Biol Int 24:263–272. doi:10.1006/cbir.2000.0499

    Article  PubMed  CAS  Google Scholar 

  • Vyas DR, Spangenburg EE, Abraha TW, Childs TE, Booth FW (2002) GSK-3β negatively regulates skeletal myotube hypertrophy. Am J Physiol Cell Physiol 283:C545–C551

    PubMed  CAS  Google Scholar 

  • White TP, Esser KA (1989) Satellite cell and growth factor involvement in skeletal muscle growth. Med Sci Sports Exerc 21:158–163. doi:10.1249/00005768-198910001-00007

    Google Scholar 

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Acknowledgments

Authors thank Dr. H. Tanaka from Department of Developmental Neurobiology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University for supplying the Pax7 antibody. This study was supported, in part, by Grant-in-Aid for Scientific Research B (20300218, KG), A (18200042, TY), and S (19100009, YO) from Japan Society for the Promotion of Science, Ground-based Research Program for Space Utilization from Japan Space Forum (KG), and Research Grant from KAO Health Science Research (KG).

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Authors and Affiliations

  1. Department of Physiology, St Marianna University School of Medicine, Kawasaki, 216–8511, Japan

    Toshihito Naito, Katsumasa Goto, Shigeta Morioka, Tatsuo Akema & Toshitada Yoshioka

  2. Department of Orthopaedic Surgery, St Marianna University School of Medicine, Kawasaki, 216-8511, Japan

    Toshihito Naito, Shigeta Morioka, Yusuke Matsuba & Moroe Beppu

  3. Laboratory of Physiology, Toyohashi SOZO University, 20-1 Matsushita, Ushikawa, Toyohashi, 440-8511, Japan

    Katsumasa Goto

  4. Faculty of Education, Yamaguchi University, Yamaguchi, 753-8513, Japan

    Takao Sugiura

  5. Graduate School of Medicine, Osaka University, Toyonaka, 560-0043, Japan

    Yoshinobu Ohira

  6. Hirosaki Gakuin University, Hirosaki, 036-8577, Japan

    Toshitada Yoshioka

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  1. Toshihito Naito
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Correspondence to Katsumasa Goto.

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Naito, T., Goto, K., Morioka, S. et al. Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3αβ signals. Eur J Appl Physiol 105, 643–651 (2009). https://doi.org/10.1007/s00421-008-0946-9

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  • DOI: https://doi.org/10.1007/s00421-008-0946-9

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