JNK/P38 mitogen-activated protein kinase used for hepatocyte growth factor-induced proliferation, differentiation, and migration in human dental papilla cells.
JNK/P38 mitogen-activated protein kinase used for hepatocyte growth factor-induced proliferation, differentiation, and migration in human dental papilla cells.
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DOI：
10.1016/j.joen.2012.06.011
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发表时间：
2012-09
影响因子：
4.2
通讯作者：
Yingying Su;Wenbo Xie;Chenglin Wang;Li Peng;Xuedong Zhou;L. Ye
中科院分区：
文献类型：
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作者：
Yingying Su;Wenbo Xie;Chenglin Wang;Li Peng;Xuedong Zhou;L. Ye
肝细胞生长因子（HGF）是一种多功能细胞因子，能够刺激多种细胞内信号通路，在广泛的细胞类型中诱导多种显著的生物活性。HGF在调节间充质干细胞多种生物反应中的作用已有报道，我们前期的研究也证实了HGF对小鼠牙乳头细胞具有促进作用。然而，所涉及的潜在机制尚不清楚。本研究研究了HGF在人牙乳头细胞（hDPCs）中使用的信号通路，以确定丝裂原活化蛋白激酶（MAPK）通路在诱导细胞增殖、分化和迁移中的作用。方法采用phospho-P38和phospho-JNK特异性抗体分析P38激酶和JNK的活化情况。采用细胞计数试剂盒-8 (Cell Counting Kit-8) WST-8法检测hDPCS的增殖，采用碱性磷酸酶活性和矿化法检测细胞分化，采用体外伤口愈合和transwell迁移法研究细胞迁移。免疫荧光染色显示纤维肌动蛋白（F-actin）。结果shgf激活了hDPCs中JNK和P38 MAPK通路。阻断hDPCs中JNK或P38通路可显著降低细胞增殖、碱性磷酸酶活性以及HGF诱导的矿物结节形成。JNK和P38抑制剂也影响HGF刺激的f -肌动蛋白重塑，从而促进HGF诱导的hDPCs迁移。结论本研究数据表明，hgf诱导的hDPCs生物学反应需要JNK和P38 MAPK通路。
INTRODUCTIONHepatocyte growth factor (HGF) is a multifunctional cytokine that is able to stimulate multiple intracellular signaling pathways to induce a remarkable variety of biological activities in a wide spectrum of cell types. The functions of HGF in modulating diverse biological responses in mesenchymal stem cells have been reported, and our previous study also demonstrated that HGF exerts promoting functions on murine dental papilla cells. However, the potential mechanisms involved are not yet clearly understood. This study investigated the signaling pathway used by HGF in human dental papilla cells (hDPCs) to identify the role of mitogen-activated protein kinase (MAPK) pathways in inducing cell proliferation, differentiation, and migration.METHODSThe activation of P38 kinase and Jun N-terminal kinase (JNK) was analyzed by using specific antibodies against phospho-P38 and phospho-JNK. Proliferation of hDPCS was measured using the WST-8 assay with Cell Counting Kit-8, cell differentiation was determined by using alkaline phosphatase activity and mineralization assays, and migration was investigated by in vitro wound healing and transwell migration assays. Immunofluorescence staining was used to visualize fibrous actin (F-actin).RESULTSHGF activated JNK and P38 MAPK pathways in hDPCs. Blockage of JNK or P38 pathway in hDPCs significantly reduced cell proliferation, alkaline phosphatase activities, as well as mineral nodule formation induced by HGF. The JNK and P38 inhibitors also influenced F-actin remodeling stimulated by HGF and thus contributed to HGF-induced hDPCs migration.CONCLUSIONSData from this study indicated that JNK and P38 MAPK pathways are required in HGF-induced biological responses in hDPCs.