MMP-9 controls Schwann cell proliferation and phenotypic remodeling via IGF-1 and ErbB receptor-mediated activation of MEK/ERK pathway.
MMP-9 controls Schwann cell proliferation and phenotypic remodeling via IGF-1 and ErbB receptor-mediated activation of MEK/ERK pathway.
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DOI：
10.1002/glia.20851
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发表时间：
2009-09
期刊：
影响因子：
6.2
通讯作者：
Shubayev, Veronica I.
中科院分区：
文献类型：
--
作者：
Chattopadhyay, Sharmila;Shubayev, Veronica I.
雪旺细胞的表型重塑是确保受损外周轴突成功再生的必要条件。神经损伤后，雪旺细胞产生的金属蛋白酶-9(MMP9)增加100倍以上，使用MMP抑制剂治疗增加了损伤神经中驻留(但不是浸润性)细胞的数量。在这里，我们证明了基质金属蛋白酶-9调节雪旺细胞的增殖和营养信号。对−/−小鼠坐骨神经切断后的体内BrdU掺入研究发现，与野生型小鼠相比，再生残肢(近端)雪旺细胞有丝分裂增加。重组基质金属蛋白酶-9抑制原代培养雪旺细胞的生长和促有丝分裂活性，并产生剂量依赖性、双相和选择性激活ERK1/2，但不能激活JNK和p38MAPK。基质金属蛋白酶-9可诱导未分化和分化雪旺细胞ERK1/2信号转导。利用MEK和营养性酪氨酸激酶受体的抑制剂，我们证实了基质金属蛋白酶-9通过IGF-1、ErbB和PDGF受体调节Ras/Raf/MEK-ERK通路。我们还报道了神经切断后早期(24小时内)基质金属蛋白酶-9基因表达的变化。这些研究表明，基质金属蛋白酶-9控制着关键的营养信号转导通路和雪旺细胞的表型重塑。
Phenotypic remodeling of Schwann cells is required to ensure successful regeneration of damaged peripheral axons. After nerve damage, Schwann cells produce an over 100-fold increase in metalloproteinase-9 (MMP-9), and therapy with an MMP inhibitor increases the number of resident (but not infiltrating) cells in injured nerve. Here, we demonstrate that MMP-9 regulates proliferation and trophic signaling of Schwann cells. Using in vivo BrdU incorporation studies of axotomized sciatic nerves of MMP-9−/− mice, we found increased Schwann cell mitosis in regenerating (proximal) stump relative to wild-type mice. Treatment of cultured primary Schwann cells with recombinant MMP-9 suppressed their growth, mitogenic activity and produced a dose-dependent, biphasic and selective activation of ERK1/2, but not JNK and p38 MAPK. MMP-9 induced ERK1/2 signaling in both undifferentiated and differentiated (using dbcAMP) Schwann cells. Using inhibitors to MEK and trophic tyrosine kinase receptors, we established that MMP-9 regulates Ras/Raf/MEK - ERK pathways through IGF-1, ErbB and PDGF receptors. We also report on the early changes of MMP-9 mRNA expression (within 24 h) after axotomy. These studies establish that MMP-9 controls critical trophic signal transduction pathways and phenotypic remodeling of Schwann cells.
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DOI：
10.1073/pnas.85.5.1701
发表时间：
1988-03-01
影响因子：
11.1
作者：
BAICHWAL, RR;BIGBEE, JW;DEVRIES, GH
通讯作者：
DEVRIES, GH
影响因子：
--
作者：
Dempsey, Peter J;Garton, Kyle;Raines, Elaine W
通讯作者：
Raines, Elaine W
影响因子：
3.5
作者：
Kobayashi, Hideo;Chattopadhyay, Sharmila;Kato, Kinshi;Dolkas, Jennifer;Kikuchi, Shin-ichi;Myers, Robert R.;Shubayev, Veronica I.
通讯作者：
Shubayev, Veronica I.
DOI：
10.1007/bf01206661
发表时间：
1989-04-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
CLEMENCE, A;MIRSKY, R;JESSEN, KR
通讯作者：
JESSEN, KR
影响因子：
15.1
作者：
Chattopadhyay, Sharmila;Myers, Robert R.;Shubayev, Veronica
通讯作者：
Shubayev, Veronica