首页> 外文期刊>Life sciences >Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, and tensin signaling.
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Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, and tensin signaling.

机译:非甾体类抗炎药通过干扰肌动蛋白,Src,FAK和张力蛋白信号传导来抑制受伤的胃单层细胞重新上皮形成。

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摘要

Re-epithelialization is essential for gastrointestinal ulcer and cutaneous wound healing. It requires epithelial cell migration and proliferation, processes that are stimulated by epidermal growth factor (EGF), and dependent on the cell cytoskeleton. Activation of Src and focal adhesion kinase (FAK) has been implicated in EGF-stimulated cell migration. Nonsteroidal anti-inflammatory drugs (NSAIDs) (both nonselective and Cox2-selective) interfere with ulcer healing and re-epithelialization in vitro and in vivo, but the cellular targets and mechanisms remain unexplored forming the basis of this study. Using a wounded gastric epithelial cell monolayer model, we demonstrated that NSAIDs reduce both basal and epidermal growth factor (EGF)-induced re-epithelialization, and that this action involves disruption of actin stress fiber formation, reduced c-Src activity, decreased phosphorylation of focal adhesion kinase (FAK), tensin and their cellular re-distribution. There was a strong correlation between NSAIDs-mediated inhibitory effect on re-epithelialization and loss of stress fibers and reduced tensin signal. Furthermore, NSAIDs significantly reduced EGF-stimulated c-Src association with FAK. These findings suggest that NSAIDs can directly affect the cell cytoskeleton and signaling pathways essential for re-epithelialization.
机译:重新上皮化对于胃肠道溃疡和皮肤伤口愈合至关重要。它需要上皮细胞迁移和增殖,受表皮生长因子(EGF)刺激的过程,并依赖于细胞的细胞骨架。 Src和粘着斑激酶(FAK)的激活与EGF刺激的细胞迁移有关。非甾体类抗炎药(NSAIDs)(非选择性和Cox2选择性)在体外和体内均会影响溃疡愈合和上皮再形成,但仍未探索细胞靶标和机制,构成了本研究的基础。使用受伤的胃上皮细胞单层模型,我们证明了NSAIDs减少了基础生长因子和表皮生长因子(EGF)诱导的上皮再生,并且该作用涉及肌动蛋白应激纤维形成的破坏,c-Src活性的降低,磷酸化的降低。粘着斑激酶(FAK),肌腱蛋白及其细胞再分布。 NSAIDs介导的对上皮再生的抑制作用与应力纤维的丧失和张力蛋白信号的减少之间存在密切的相关性。此外,NSAIDs显着降低了EGF刺激的c-Src与FAK的结合。这些发现表明,NSAID可以直接影响重新上皮形成所必需的细胞骨架和信号通路。

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