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首页> 外文期刊>Molecular and Cellular Biology >Two Independent Signaling Pathways Mediate the Antiapoptotic Action of Macrophage-Stimulating Protein on Epithelial Cells
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Two Independent Signaling Pathways Mediate the Antiapoptotic Action of Macrophage-Stimulating Protein on Epithelial Cells

机译：两种独立的信号通路介导巨噬细胞刺激蛋白对上皮细胞的抗凋亡作用

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In addition to its effects on macrophage function, macrophage-stimulating protein (MSP) is a growth and motility factor for epithelial cells. The growth and survival of epithelial cells generally require two signals, one generated by interaction with extracellular matrix via integrins, the other initiated by a growth factor. Therefore we investigated the effect of MSP on epithelial cell survival. Survival of epithelial cells cultured overnight in serum-free medium was promoted by adhesion, which activated both the phosphatidylinositol 3′-kinase (PI3-K)/AKT and mitogen-activated protein kinase (MAPK) pathways, operating independently of one another. The number of apoptotic cells resulting from inhibition of either pathway alone was approximately doubled by simultaneous inhibition of both pathways. This shows that each pathway made a partial contribution to the prevention of apoptosis. In the presence of an inhibitor of either pathway, MSP increased the activity of the other pathway so that the single uninhibited pathway alone was sufficient to prevent apoptosis. In contrast to the results with adherent cells, although MSP also prevented apoptosis of cells in suspension (anoikis), its effect was mediated only by the PI3-K/AKT pathway. Despite activation of MAPK by MSP, anoikis was not prevented in suspended cells with a blocked PI3-K/AKT pathway. Thus, activation of MAPK alone is not sufficient to mediate MSP antiapoptotic effects. Cell adhesion generates an additional signal, which is essential for MSP to use MAPK in an antiapoptotic pathway. This may involve translocation of MSP-activated MAPK from the cytoplasm into the nucleus, which occurs only in adherent cells. Our results suggest that there is cross talk between cell matrix adhesion and growth factors in the regulation of cell survival via the MAPK pathway. Growth factors induce MAPK activation, and adhesion mediates MAPK translocation from the cytoplasm into the nucleus.
机译：除了对巨噬细胞功能的影响外，巨噬细胞刺激蛋白（MSP）是上皮细胞的生长和运动因子。上皮细胞的生长和存活通常需要两个信号，一个信号是通过整联蛋白与细胞外基质相互作用而产生的，另一个是由生长因子引发的。因此，我们研究了MSP对上皮细胞存活的影响。粘附促进了在无血清培养基中过夜培养的上皮细胞的存活，该粘附激活了磷脂酰肌醇3'-激酶（PI3-K）/ AKT和有丝分裂原激活的蛋白激酶（MAPK）途径，彼此独立。通过同时抑制两种途径，单独抑制任一途径而导致的凋亡细胞数量大约增加了一倍。这表明每种途径对细胞凋亡的预防都有部分贡献。在任一途径的抑制剂均存在的情况下，MSP会增加另一途径的活性，以使单个不受抑制的途径足以阻止细胞凋亡。与贴壁细胞的结果相反，尽管MSP还能阻止悬浮细胞的细胞凋亡（无神经），但其作用仅由PI3-K / AKT途径介导。尽管MSP激活了MAPK，但在PI3-K / AKT途径受阻的悬浮细胞中，仍未预防失神经。因此，单独激活MAPK不足以介导MSP抗凋亡作用。细胞粘附会产生额外的信号，这对于MSP在抗凋亡途径中使用MAPK至关重要。这可能涉及MSP激活的MAPK从细胞质转移到细胞核中，仅在粘附细胞中发生。我们的结果表明，通过MAPK途径调节细胞存活的过程中，细胞基质粘附与生长因子之间存在串扰。生长因子诱导MAPK活化，粘附作用介导MAPK从细胞质进入细胞核。

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