Apelin receptor (Aplnr) signaling promotes fibroblast migration
Apelin receptor (Aplnr) signaling promotes fibroblast migration
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DOI：
10.1016/j.tice.2019.01.003
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发表时间：
2019-02-01
期刊：
影响因子：
2.6
通讯作者：
Dogan, Aysegul
中科院分区：
文献类型：
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作者：
Dogan, Aysegul
细胞迁移是发育、组织再生、伤口愈合、癌症和免疫功能中的主要细胞过程之一。成纤维细胞迁移和基质相互作用背后的潜在分子机制产生了组织稳态的基础。Apelin受体（Apelin receptor，Aplnr）信号在原肠胚形成运动中的作用近年来逐渐被发现，但Aplnr如何调节细胞运动尚不清楚。在目前的研究中，Aplnr信号转导的迁移活动已被证明在体外培养的成纤维细胞通过划痕试验，基因和蛋白质表达分析。在MEFs和NIH-3 T3小鼠成纤维细胞中激活并敲低Aplnr信号传导，以分析细胞迁移是否受到Aplnr信号传导的影响。Apelin肽和小分子ML-233激活Aplnr信号传导增加细胞运动和迁移相关基因和蛋白质（包括肌动蛋白和波形蛋白）的表达。类似地，通过siRNA暴露降低Aplnr和爱帕琳（Apln）的表达抑制小鼠成纤维细胞的细胞迁移。与对照相比，将爱帕琳肽和小分子ML-233应用于人成纤维细胞显著提高了划痕闭合率。本研究证明Aplnr信号传导的激活促进体外成纤维细胞的细胞迁移。Aplnr信号可能是一个潜在的治疗候选者，作为癌症和伤口愈合的迁移相关的调节机制，供进一步研究。
Cell migration is one of the major cellular processes in development, tissue regeneration, wound healing, cancer and immune function. Underlying molecular mechanism behind the fibroblast cell migration and matrix interactions generates the basis of tissue homeostasis. The role of Apelin receptor (Aplnr) signaling in gastrulation movements has emerged in recent years but how Aplnr regulates cell movement remains unclear. In the current study, the migratory activity of Aplnr signaling has been shown in cultured fibroblast cells in vitro by scratch assay, gene and protein expression analyses. Aplnr signaling was activated and knocked down in MEFs and NIH-3T3 mouse fibroblast cells to analyze whether cell migration is affected by Aplnr signalling. Activation of Aplnr signaling by Apelin peptide and small molecule ML-233 increased cell movement and expression of migration related gene and proteins including Actin and Vimentin. Similarly, reducing the expression of Aplnr and Apelin (Apln) by siRNA exposure inhibited cell migration of mouse fibroblast cells. Application of Apelin peptide and small molecule ML-233 to human fibroblast cells enhanced scratch closure rate significantly compared to control. This study demonstrated that activation of Aplnr signaling promotes cell migration of fibroblast cells in vitro. Aplnr signaling could be a potential therapeutic candidate as a migration related regulatory mechanism in cancer and wound healing for further research.