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

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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)

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