Apelin receptor (Aplnr) signaling promotes fibroblast migration.

Abstract

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.