演題詳細
Poster
情報伝達とその調節
Signal Transduction and Modulation
| 開催日 | 2014/9/12 |
|---|---|
| 時間 | 11:00 - 12:00 |
| 会場 | Poster / Exhibition（Event Hall B） |
TGF-βはペリサイトからのマトリックスメタロプロテアーゼー9の遊離を促進する
Transforming-growth factor-β induces matrix metalloproteinase-9 activation in human brain pericyte
- P2-055
- 高橋 揚子 / Yoko Takahashi:1 眞木 崇州 / Takakuni Maki:2 大隅 典子 / Noriko Osumi:1 荒井 健 / Ken Arai:2
- 1:東北大院医創生応用医セ発生発達神経 / Dept Dev Neurosci, Tohoku Uni, Miyagi, Japan 2:Neuroprotection Res Lab, Dep Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School / Neuroprotection Res Lab, Dep Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School
Transforming-growth factor-βinduces matrix metalloproteinase-9 activation in human brain pericyte
Yoko Takahashi1,2, Takakuni Maki2, Noriko Osumi1, and Ken Arai2
1 Department of Developmental Neuroscience, Tohoku University School of Medicine
2Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School
Pericytes are vascular mural cells embedded within the basement membrane of blood microvessels. Accumulating evidence indicates that pericytes are involved in modulating various aspects of neurovascular homeostasis by secreting soluble factors. However, little is known about their regulatory signaling pathways in brain pericytes. Here we report that p38 mitogen-activated protein kinase (MAPK) plays an essential role in transforming growth factor-β (TGF-β)-induced matrix metalloproateinase-9 (MMP-9) secretion. Cultured human brain vascular pericytes were treated with purified human TGF-β1 (0.1- 10 ng/mL for 24 hours). TGF-β1 increased the MMP-9 level in culture media in a concentration dependent manner as measured by gelatin zymography. WST assay confirmed that TGF-β1 did not affect cell survival of the brain pericytes. Immunostaining showed that the brain pericytes expressed TGF-β-receptor, and co-treatment of the pericytes with a TGF-β-receptor inhibitor SB431542 (0.5 - 5 uM) decreased the TGF-β1-induced MMP-9 upregulation. In addition, a p38 MAPK inhibitor SB203580 (0.5 - 5 uM) also canceled the effect of TGF-β1 in MMP-9 expression in pericytes. Western blotting confirmed that TGF-β1 treatment increased the level of p38 MAPK phosphorylation, and once again, co-treatment of SB431542 blocked the TGF-β1-induced phosphorylation of p38 MAPK. Both TGF-β and MMP-9 are major neurovascular mediators, and therefore, our current finding may suggest a novel mechanism by which pericytes regulate neurovascular homeostasis.
Acknowledgements: This work was supported by Japan Society for the Promotion of Science (T. M.), and National Institutes of Health (K.A.).