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http://asiair.asia.edu.tw/ir/handle/310904400/112988
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| Title: | Lipopolysaccharide-Induced Matrix Metalloproteinase-9 Expression Associated with Cell Migration in Rat Brain Astrocytes. |
| Authors: | 楊建中;Yang, Chien-Chung;林志中;Lin, Chih-Chung;蕭立德;Hsiao, Li-Der;郭景銘;Kuo, Jing-Ming;曾惠卿;Tsen, Hui-Ching;楊春茂;Yang, Chuen-Mao |
| Contributors: | 學士後獸醫學系 |
| Keywords: | LPS;MMP-9;astrocytes;neurodegeneration;neuroinflammation. |
| Date: | 2019-12 |
| Issue Date: | 2020-09-07 05:32:33 (UTC+0) |
| Publisher: | 亞洲大學 |
| Abstract: | Neuroinflammation is a landmark of neuroinflammatory and neurodegenerative diseases. Matrix metalloproteinase (MMP)-9, one member of MMPs, has been shown to contribute to the pathology of these brain diseases. Several experimental models have demonstrated that lipopolysaccharide (LPS) exerts a pathological role through Toll-like receptors (TLRs) in neuroinflammation and neurodegeneration. However, the mechanisms underlying LPS-induced MMP-9 expression in rat brain astrocytes (RBA-1) are not completely understood. Here, we applied pharmacological inhibitors and siRNA transfection to assess the levels of MMP-9 protein, mRNA, and promoter activity, as well as protein kinase phosphorylation in RBA-1 cells triggered by LPS. We found that LPS-induced expression of pro-form MMP-9 and cell migration were mediated through TLR4, proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), platelet-derived growth factor receptor (PDGFR), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), and Jun amino-terminal kinase (JNK)1/2 signaling molecules in RBA-1 cells. In addition, LPS-stimulated binding of c-Jun to the MMP-9 promoter was confirmed by chromatin immunoprecipitation (ChIP) assay, which was blocked by pretreatment with c-Src inhibitor II, PF431396, AG1296, LY294002, Akt inhibitor VIII, p38 MAP kinase inhibitor VIII, SP600125, and tanshinone IIA. These results suggest that in RBA-1 cells, LPS activates a TLR4/c-Src/Pyk2/PDGFR/PI3K/Akt/p38 MAPK and JNK1/2 pathway, which in turn triggers activator protein 1 (AP-1) activation and ultimately induces MMP-9 expression and cell migration. |
| Relation: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |
| Appears in Collections: | [學士後獸醫學系] 期刊論文
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