Transforming growth factor-beta1 induces matrix metalloproteinase-9 expression in human meningeal cells via ERK and Smad pathways.
Transforming growth factor (TGF)-beta1, a cytokine released into the cerebrospinal fluid (CSF) after intraventricular hemorrhage (IVH), stimulates the expression of the components of the extracellular matrix (ECM), which causes progressive ventricular dilatation by impaired CSF absorption. Matrix metalloproteinase-9 (MMP-9), a proteinase involved in the removal of ECM proteins, has been shown to contribute to the resolution of progressive ventricular dilation after IVH. The aim of this study is to clarify the mechanism by which MMP-9 is expressed following IVH. Cultured human meningeal cells were treated with human recombinant TGF-beta1. RT-PCR demonstrated that TGF-beta1 induced MMP-9 expression in the meningeal cells in a dose-dependent manner. The TGF-beta1-induced MMP-9 expression was attenuated in the presence of either MEK or Smad 3 inhibitor. Our data indicated that MMP-9 is released into the CSF from meningeal cells in response to TGF-beta1, most probably through the activation of ERK and Smad pathways.
Department of Pediatrics, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. toshio5p@asahikawa-med.ac.jp
Toshio
T
Okamoto
Satoru
S
Takahashi
Eiki
E
Nakamura
Ken
K
Nagaya
Tokitsugi
T
Hayashi
Kenji
K
Fujieda
D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008578:Meninges / Q000187:drug effects* / Q000201:enzymology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology* / Q000502:physiology
C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9