Granulocyte Colony-Stimulating Factor and Its Potential Application for Skeletal Muscle Repair and Regeneration

Granulocyte colony-stimulating factor (G-CSF) was originally discovered in the context of hematopoiesis. However, the identification of the G-CSF receptor (G-CSFR) being expressed outside the hematopoietic system has revealed wider roles for G-CSF, particularly in tissue repair and regeneration. Skeletal muscle damage, including that following strenuous exercise, induces an elevation in plasma G-CSF, implicating it as a potential mediator of skeletal muscle repair. This has been supported by preclinical studies and clinical trials investigating G-CSF as a potential therapeutic agent in relevant disease states. This review focuses on the growing literature associated with G-CSF and G-CSFR in skeletal muscle under healthy and disease conditions and highlights the current controversies.

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Granulocyte colony-stimulating factor potential use in the treatment of children with cerebral palsy

Progress in Health Sciences ◽

10.5604/01.3001.0010.1882 ◽

2017 ◽

Vol 7 (1) ◽

pp. 0-0

Author(s):

G. Paszko-Patej ◽

D. Sienkiewicz ◽

B. Okurowska-Zawada ◽

W. Kułak

Keyword(s):

Cerebral Palsy ◽

Tissue Repair ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Neuroprotective Actions ◽

Apoptosis And Inflammation ◽

Brain And Spinal Cord ◽

The Brain ◽

Stimulating Factor ◽

Potential Use

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the blood. Recent studies demonstrated the presence of CSF-receptor (G-CSFR) system in the brain and spinal cord, and their roles in neuroprotection and neural tissue repair, as well as improvement in functional recovery. G-CSF exerts neuroprotective actions through the inhibition of apoptosis and inflammation, and the stimulation of neurogenesis. This review highlights recent studies on the potential use of G-CSF in cerebral palsy.

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Regulation of Granulocyte Colony-Stimulating Factor and Its Receptor in Skeletal Muscle Is Dependent Upon the Type of Inflammatory Stimulus

Journal of Interferon & Cytokine Research ◽

10.1089/jir.2014.0159 ◽

2015 ◽

Vol 35 (9) ◽

pp. 710-719 ◽

Cited By ~ 11

Author(s):

Craig Robert Wright ◽

Erin Louise Brown ◽

Paul A. Della Gatta ◽

Ioannis G. Fatouros ◽

Leonidas G. Karagounis ◽

...

Keyword(s):

Skeletal Muscle ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Inflammatory Stimulus ◽

Stimulating Factor

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Granulocyte-colony stimulating factor enhances muscle proliferation and strength following skeletal muscle injury in rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00066.2007 ◽

2007 ◽

Vol 103 (5) ◽

pp. 1857-1863 ◽

Cited By ~ 44

Author(s):

Ioannis Stratos ◽

Robert Rotter ◽

Christian Eipel ◽

Thomas Mittlmeier ◽

Brigitte Vollmar

Keyword(s):

Skeletal Muscle ◽

Cell Proliferation ◽

Muscle Strength ◽

Muscle Regeneration ◽

Muscle Injury ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Tetanic Force ◽

Twitch Force ◽

Stimulating Factor

Insufficiency of skeletal muscle regeneration often impedes the healing process with functional deficiencies and scar formation. We tested the hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) with respect to its efficacy to improve functional muscle regeneration following skeletal muscle injury in Wistar rats. After crush injury to the left soleus muscle, animals received daily G-CSF (20 μg/kg ip) or vehicle solution ( n = 30 per group each). Sham-operated animals without muscle injury served as controls ( n = 15). After in vivo assessment of the fast-twitch and tetanic contraction capacity of the soleus muscles at days 4, 7, and 14 post-injury, sampling of muscle tissue served for analysis of satellite cell proliferation [bromodeoxyuridine (BrdU)/laminin and BrdU/desmin double immunohistochemistry] and cell apoptosis (transferase nick-end labeling analysis). Muscle strength analysis revealed recovery of contraction forces to 26 ± 2, 35 ± 3, and 53 ± 3% (twitch force) and to 20 ± 3, 24 ± 2, and 37 ± 2% (tetanic force) within the 14-day observation period in vehicle-treated animals. In contrast, G-CSF increased contractile forces with markedly higher values at day 7 (twitch force: 42 ± 2%; tetanic force: 34 ± 2%) and day 14 (twitch force: 62 ± 3%; tetanic force: 43 ± 3%). This enhancement of muscle function was preceded by a significant increase of satellite cell proliferation (BrdU-positive cells/mm2: 27 ± 6 vs. vehicle: 12 ± 3) and a moderate decrease of cell apoptosis (transferase nick-end labeling-positive cells/mm2: 11 ± 2 vs. vehicle: 16 ± 3) at day 4. In conclusion, G-CSF histologically promoted viability and proliferation of muscle cells and functionally enhanced recovery of muscle strength. Thus G-CSF might represent a therapeutic option to optimize the posttraumatic course of muscle tissue healing.

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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

European Journal of Applied Physiology ◽

10.1007/s00421-008-0946-9 ◽

2008 ◽

Vol 105 (4) ◽

pp. 643-651 ◽

Cited By ~ 18

Author(s):

Toshihito Naito ◽

Katsumasa Goto ◽

Shigeta Morioka ◽

Yusuke Matsuba ◽

Tatsuo Akema ◽

...

Keyword(s):

Skeletal Muscle ◽

Regenerative Process ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor

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Granulocyte Colony-Stimulating Factor Does Not Influence Clostridium Perfringens α-Toxin-Induced Myonecrosis in Mice

Toxins ◽

10.3390/toxins11090509 ◽

2019 ◽

Vol 11 (9) ◽

pp. 509 ◽

Cited By ~ 2

Author(s):

Masaya Takehara ◽

Yuuta Sonobe ◽

Hiroto Bandou ◽

Keiko Kobayashi ◽

Masahiro Nagahama

Keyword(s):

Skeletal Muscle ◽

Clostridium Perfringens ◽

Tissue Injury ◽

Type A ◽

Creatine Kinase Activity ◽

Dependent Manner ◽

Protective Effects ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor

Clostridium perfringens type A causes gas gangrene characterized by myonecrosis and development of an effective therapy for treating affected patients is of clinical importance. It was recently reported that the expression of granulocyte colony-stimulating factor (G-CSF) is greatly up-regulated by C. perfringens infection. However, the role of G-CSF in C. perfringens-mediated myonecrosis is still unclear. Here, we assessed the destructive changes in C. perfringens-infected skeletal muscles and tested whether inhibition of G-CSF receptor (G-CSFR) signaling or administration of recombinant G-CSF affects the tissue injury. Severe edema, contraction of muscle fiber diameter, and increased plasma creatine kinase activity were observed in mice intramuscularly injected with C. perfringens type A, and the destructive changes were α-toxin-dependent, indicating that infection induces the destruction of skeletal muscle in an α-toxin-dependent manner. G-CSF plays important roles in the protection of tissue against damage and in the regeneration of injured tissue. However, administration of a neutralizing antibody against G-CSFR had no profound impact on the destructive changes to skeletal muscle. Moreover, administration of recombinant human G-CSF, filgrastim, imparted no inhibitory effect against the destructive changes caused by C. perfringens. Together, these results indicate that G-CSF is not beneficial for treating C. perfringens α-toxin-mediated myonecrosis, but highlight the importance of revealing the mechanism by which C. perfringens negates the protective effects of G-CSF in skeletal muscle.

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