Lipopolysaccharide Stimulated the Migration of NIH3T3 Cells Through a Positive Feedback Between β-Catenin and COX-2
Lipopolysaccharide Stimulated the Migration of NIH3T3 Cells Through a Positive Feedback Between β-Catenin and COX-2
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脂多糖通过 β-连环蛋白和 COX-2 之间的正反馈刺激 NIH3T3 细胞的迁移
DOI：
10.3389/fphar.2018.01487
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发表时间：
2018-12-19
影响因子：
5.6
通讯作者：
Tang, He-Bin
中科院分区：
文献类型：
--
作者：
Li, Xiao-Jun;Huang, Feng-Zhen;Tang, He-Bin
β -连环蛋白/COX-2如何促进炎症诱导的成纤维细胞迁移仍然知之甚少。因此，本研究采用脂多糖（LPS）作为刺激物，加速NIH3T3细胞的迁移，模拟组织修复过程。LPS处理使细胞迁移呈浓度和时间依赖性。COX-2抑制剂NS398抑制lps诱导的NIH3T3细胞迁移。DKK-1是Wnt/ β -连环蛋白信号的拮抗剂，也能抑制这种迁移。然而，通过GSK-3 β诱导β -连环蛋白的TWS119增加了细胞迁移。LPS或TWS119处理可增加COX-2、β -catenin、tgf - β 1和HMGB-1的表达，添加NS398或DKK-1可减弱这些表达。LPS诱导PGE(2)产生，PGE(2)增加β -catenin的表达和核易位，而EP2阻滞剂AH6809减轻了这种作用。TWS119增加了COX-2启动子中荧光素酶的活性。综上所述，LPS通过b-catenin与COX-2之间的正反馈作用刺激NIH3T3成纤维细胞迁移，其中PGE(2)、EP2、tgf - β 1和HMGB-1作为信号分子。
How beta-catenin/COX-2 contribute to inflammation- induced fibroblasts migration remains poorly understood. Therefore, in this study, lipopolysaccharide (LPS) was used as a stimulus to accelerate the migration of NIH3T3 cells, which mimicked the tissue repair process. LPS treatment increased the cell migration in concentration-and time-dependent manner. And NS398, a COX-2 inhibitor, inhibited LPS-induced NIH3T3 cells migration. DKK-1, an antagonist of the Wnt/beta-catenin signaling, also inhibited that migration. However, TWS119, an inducer of beta-catenin via GSK-3 beta, increased the cell migration. LPS or TWS119 treatment increased COX-2, beta-catenin, TGF-beta 1, and HMGB-1 expressions, and that could be attenuated by NS398 or DKK-1 addition. LPS induced the PGE(2) production, and PGE(2) increased the expression and nuclear translocation of beta-catenin, while EP2 blocker, AH6809, alleviated those effects. TWS119 increased the luciferase activity in the COX-2 promoter. In conclusion, LPS stimulated the NIH3T3 fibroblasts migration through a positive feedback between b-catenin and COX-2, in which PGE(2), EP2, TGF-beta 1, and HMGB-1 played as signal molecules.