GM-CSF reduces expression of chondroitin sulfate proteoglycan (CSPG) core proteins in TGF-β-treated primary astrocytes
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
GM-CSF plays a role in the nervous system, particularly in casesof injury. A therapeutic effect of GM-CSF has been reportedin rat models of various central nervous system injuries. Wepreviously showed that GM-CSF could enhance long-term recoveryin a rat spinal cord injury model, inhibiting glial scarformation and increasing the integrity of axonal structure. Here, we investigated molecular the mechanism(s) by whichGM-CSF suppressed glial scar formation in an in vitro systemusing primary astrocytes treated with TGF-β. GM-CSF repressedthe expression of chondroitin sulfate proteoglycan(CSPG) core proteins in astrocytes treated with TGF-β. GM-CSFalso inhibited the TGF-β-induced Rho-ROCK pathway, whichis important in CSPG expression. Finally, the inhibitory effectof GM-CSF was blocked by a JAK inhibitor. These results mayprovide the basis for GM-CSF’s effects in glial scar inhibitionand ultimately for its therapeutic effect on neural cell injuries.
Abstract
GM-CSF plays a role in the nervous system, particularly in casesof injury. A therapeutic effect of GM-CSF has been reportedin rat models of various central nervous system injuries. Wepreviously showed that GM-CSF could enhance long-term recoveryin a rat spinal cord injury model, inhibiting glial scarformation and increasing the integrity of axonal structure. Here, we investigated molecular the mechanism(s) by whichGM-CSF suppressed glial scar formation in an in vitro systemusing primary astrocytes treated with TGF-β. GM-CSF repressedthe expression of chondroitin sulfate proteoglycan(CSPG) core proteins in astrocytes treated with TGF-β. GM-CSFalso inhibited the TGF-β-induced Rho-ROCK pathway, whichis important in CSPG expression. Finally, the inhibitory effectof GM-CSF was blocked by a JAK inhibitor. These results mayprovide the basis for GM-CSF’s effects in glial scar inhibitionand ultimately for its therapeutic effect on neural cell injuries.
참고문헌 (39)
- Amar, A. P., "Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury", Neurosurgery, 44, pp.1027~1039 (1999)
- Crowe, M. J., "Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys", Nat. Med, 3, pp.73~76 (1997)
- Sandvig, A., "Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration", Glia, 46, pp.225~251 (2004)
- Jones, L. L., "The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury", Exp. Neurol, 182, pp.399~411 (2003)
- Silver, J, "Regeneration beyond the glial scar", Nat. Rev. Neurosci, 5, pp.146~156 (2004)
- David, S., "Recruiting the immune response to promote axon regeneration in the injured spinal cord", Neuroscientist, 8, pp.33~41 (2002)
- Schermer, C., "Granulocyte macrophage- colony stimulating factor activates microglia in rat cortex organotypic brain slices", Neurosci. Lett, 328, pp.180~184 (2002)
- Kim, J. K., "Effects of GM-CSF on the neural progenitor cells", Neuroreport, 15, pp.2161~2165 (2004)
- Kannan, Y., "Neurotrophic action of interleukin 3 and granulocyte-macrophage colony- stimulating factor on murine sympathetic neurons", Neuroimmunomodulation, 8, pp.132~141 (2000)
- Franzen, R., "Nervous system injury: focus on the inflammatory cytokine 'granulocyte- macrophage colony stimulating factor'", Neurosci. Lett, 361, pp.76~78 (2004)
- Saada, A., "Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells", J. Cell Biol, 133, pp.159~167 (1996)
- Ousman, S. S., "MIP-1alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell response that mediates rapid phagocytosis of myelin from the adult mouse spinal cord", J. Neurosci, 21, pp.4649~4656 (2001)
- Bouhy, D., "Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages", ASEB J, 20, pp.1239~1241 (2006)
- Ha, Y., "Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury", J. Neurosurg, 2, pp.55~61 (2005)
- Park, H. C., "Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor", Tissue Engineering, 11, pp.913~922 (2005)
- Yoon, S. H., "Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I", II clinical trial, 2007, pp.25, 2066~2073
- Huang, X., "GM-CSF inhibits apoptosis of neural cells via regulating the expression of apoptosis-related proteins", Neurosci. Res, 58, pp.50~57 (2007)
- Kim, N. K., "Granulocyte-macrophage colony-stimulating factor promotes survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced murine Parkinson's disease model", European J. Neurosci, 29, pp.891~900 (2009)
- Kong, T., "Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte-macrophage colony-stimulating factor in rats. Laboratory investigation", J. Neurosurg, 111, pp.155~163 (2009)
- Huang, X., "GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury", J. Neurol. Sci, 277, pp.87~97 (2009)
- Asher, R. A., "Neurocan is upregulated in injured brain and in cytokine-treated astrocytes", J. Neurosci, 20, pp.2427~2438 (2000)
- Smith, G. M., "Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes", Glia, 52, pp.209~218 (2005)
- Monnier, P. P., "The Rho", ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar, 2003, pp.22, 319~330
- Zhang, Y. E., "Non-Smad pathways in TGF-beta signaling", Cell Res, 19, pp.128~139 (2009)
- Guthridge, M. A., "Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptors", Stem Cells, 16, pp.301~313 (1998)
- Choi, J. K., "Signal transduction pathways of GM-CSF in neural cell lines", Neurosci. Lett, 420, pp.217~222 (2007)
- Iannotti, C., "Dural repair reduces connective tissue scar invasion and cystic cavity formation after acute spinal cord laceration injury in adult rats", J. Neurotrauma, 23, pp.853~865 (2006)
- Roitbak, T., "Diffusion barriers evoked in the rat cortex by reactive astrogliosis", Glia, 28, pp.40~48 (1999)
- Hynds, D. L., "Neurite outgrowth inhibition by chondroitin sulfate proteoglycan: stalling", stopping exceeds turning in human neuroblastoma growth cones, 1999, pp.160, 244~255
- Logan, A., "Effects of transforming growth factor beta 1 on scar production in the injured central nervous system of the rat", Eur. J. Neurosci, 6, pp.355~363 (1994)
- Schwab, J. M., "Differential cellular accumulation of connective tissue growth factor defines a subset of reactive astrocytes, invading fibroblasts, and endothelial cells following central nervous system injury in rats and humans", J. Neurotrauma, 18, pp.377~388 (2001)
- Logan, A., "Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-beta2", Eur. J. Neurosci, 11, pp.2367~2374 (1999)
- John, G. R., "Interleukin- 1beta induces a reactive astroglial phenotype via deactivation of the Rho GTPase-Rock axis", J. Neurosci, 24, pp.2837~2845 (2004)
- Holmberg, E., "Statins decrease chondroitin sulfate proteoglycan expression and acute astrocyte activation in central nervous system injury", Exp. Neurol, 214, pp.78~86 (2008)
- Chan, C. C., "ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans", Glia, 55, pp.369~384 (2007)
- Gopalakrishnan, S. M., "Role of Rho kinase pathway in chondroitin sulfate proteoglycan- mediated inhibition of neurite outgrowth in PC12 cells", J. Neurosci. Res, 86, pp.2214~2226 (2008)
- Lingor, P., "Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo", J. Neurochem, 103, pp.181~189 (2007)
- Jain, A., "Modulation of Rho GTPase activity alleviates chondroitin sulfate proteoglycan-dependent inhibition of neurite extension", J. Neurosci. Res, 77, pp.299~307 (2004)
- Just, I., "Therapeutic effects of Clostridium botulinum C3 exoenzyme", Naunyn. Schmiedebergs, 383, pp.247~252 (2011)
