GM-CSF reduces expression of chondroitin sulfate proteoglycan (CSPG) core proteins in TGF-β-treated primary astrocytes

被引:14
作者
Choi, Jung-Kyoung [1 ,3 ]
Park, Sang-Yoon [3 ]
Kim, Kil Hwan [1 ]
Park, So Ra [1 ]
Lee, Seok-Geun [3 ]
Choi, Byung Hyune [2 ]
机构
[1] Inha Univ, Coll Med, Dept Physiol, Inchon 400712, South Korea
[2] Inha Univ, Coll Med, Dept Adv Biomed Sci, Inchon 400712, South Korea
[3] Kyung Hee Univ, Coll Korean Med, Canc Prevent Mat Dev Res Ctr, Dept Sci Korean Med, Seoul 130701, South Korea
基金
新加坡国家研究基金会;
关键词
CSPG core proteins; Glial scar; GM-CSF; Primary astrocytes; TGF-beta; COLONY-STIMULATING FACTOR; CENTRAL-NERVOUS-SYSTEM; MARROW-CELL TRANSPLANTATION; SPINAL-CORD; NEURITE OUTGROWTH; AXONAL REGENERATION; GROWTH-FACTOR; GLIAL SCAR; RAT CORTEX; INJURY;
D O I
10.5483/BMBRep.2014.47.12.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
GM-CSF plays a role in the nervous system, particularly in cases of injury. A therapeutic effect of GM-CSF has been reported in rat models of various central nervous system injuries. We previously showed that GM-CSF could enhance long-term recovery in a rat spinal cord injury model, inhibiting glial scar formation and increasing the integrity of axonal structure. Here, we investigated molecular the mechanism(s) by which GM-CSF suppressed glial scar formation in an in vitro system using primary astrocytes treated with TGF-beta. GM-CSF repressed the expression of chondroitin sulfate proteoglycan (CSPG) core proteins in astrocytes treated with TGF-beta. GM-CSF also inhibited the TGF-beta-induced Rho-ROCK pathway, which is important in CSPG expression. Finally, the inhibitory effect of GM-CSF was blocked by a JAK inhibitor. These results may provide the basis for GM-CSF's effects in glial scar inhibition and ultimately for its therapeutic effect on neural cell injuries.
引用
收藏
页码:679 / 684
页数:6
相关论文
共 40 条
[1]   Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury [J].
Amar, AP ;
Levy, ML .
NEUROSURGERY, 1999, 44 (05) :1027-1039
[2]  
Asher RA, 2000, J NEUROSCI, V20, P2427
[3]   Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages [J].
Bouhy, Delphine ;
Malgrange, Brigitte ;
Multon, Sylvie ;
Poirrier, Anne-Lise ;
Scholtes, Felix ;
Schoenen, Jean ;
Franzen, Rachelle .
FASEB JOURNAL, 2006, 20 (08) :1239-+
[4]   ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans [J].
Chan, Carmen C. M. ;
Wong, Angel K. ;
Liu, Jie ;
Steeves, John D. ;
Tetzlaff, Wolfram .
GLIA, 2007, 55 (04) :369-384
[5]   Signal transduction pathways of GM-CSF in neural cell lines [J].
Choi, Jung Kyoung ;
Choi, Byung Hyune ;
Ha, Yoon ;
Park, Hyeonseon ;
Yoon, Seung Hwan ;
Park, Hyung Chun ;
Park, So Ra .
NEUROSCIENCE LETTERS, 2007, 420 (03) :217-222
[6]   Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].
Crowe, MJ ;
Bresnahan, JC ;
Shuman, SL ;
Masters, JN ;
Beattie, MS .
NATURE MEDICINE, 1997, 3 (01) :73-76
[7]   Recruiting the immune response to promote axon regeneration in the injured spinal cord [J].
David, S ;
Ousman, SS .
NEUROSCIENTIST, 2002, 8 (01) :33-41
[8]   Nervous system injury: focus on the inflammatory cytokine 'granulocyte-macrophage colony stimulating factor' [J].
Franzen, R ;
Bouhy, D ;
Schoenen, J .
NEUROSCIENCE LETTERS, 2004, 361 (1-3) :76-78
[9]   Role of rho kinase pathway in chondroitin sulfate proteoglycan-mediated inhibition of neurite outgrowth in PC12 cells [J].
Gopalakrishnan, Sujatha M. ;
Teusch, Nicole ;
Imhof, Christiane ;
Bakker, Margot H. M. ;
Schurdak, Mark ;
Burns, David J. ;
Warrior, Usha .
JOURNAL OF NEUROSCIENCE RESEARCH, 2008, 86 (10) :2214-2226
[10]   Mechanism of activation of the GM-CSF IL-3, and IL-5 family of receptors [J].
Guthridge, MA ;
Stomski, FC ;
Thomas, D ;
Woodcock, JM ;
Bagley, CJ ;
Berndt, MC ;
Lopez, AF .
STEM CELLS, 1998, 16 (05) :301-313