MiR-15b-5p Mediates ICAM-1 Regulating The Expression Of FAK In Endothelial Cell

Inflammatory response is a common pathology process that organism makes a defensive response to external stimuli.Usually,the inflammatory response as an organism’s automatic defense system is beneficial to the body,but the excessive,uncontrolled inflammatory response to the organism is a great harm.The main reason for pig lung injury caused by Porcine Reproductive and Respiratory Syndrome Virus(PRRSV)infection is excessive inflammatory response.At present,there is no effective treatment for this lung injury.In the inflammation process,a large number of neutrophils is captured by pulmonary vascular endothelial,then adheres to endothelium,and eventually migrates across the endothelium,and exudates resulting in pulmonary edema by destructing the integrity and increasing permeability of the endothelium.Intercellular adhesion molecule-1(ICAM-1)plays a very important role in the process of endothelial capture,migration,activation and exudation of neutrophil.Focal adhesion kinase(FAK)can mediate cell adhesion and migration,and regulate the turnover of focal adhesion,and is also involved in the repair process after endothelial destroyed.Studies have shown that in the injured endothelium,the migration of endothelial cells significantly increased,while the degree of FAK phosphorylation significantly increased.When the activation of FAK is prevented,endothelial cell migration is subsequently blocked.This study explored the relationship between the expression of FAK and inflammation,the regulation of ICAM-1 on FAK expression,and it is expected to provide a theoretical basis for lung injury caused by PRRSV infection and other excessive inflammatory response.This study first examined the expression change of FAK in four inflammatory conditions,and the results showed a significant increase.The effect of ICAM-1 knockout on FAK expression was then examined and the expression of FAK was found to be significantly reduced.Simultaneously,we found that ICAM-1 knockout can promote the expression of miR-15b-5p,and the bioinformatics software predicts that miR-15b-5p can target the 3’UTR region of FAK.We demonstrate that miR-15b-5p is capable of targeting the 3’UTR region of FAK by dual-luciferase reporter assay.At last,miR-15b-5p is overexpressed at the cellular level,and the results show that overexpression of miR-15b-5p inhibites the expression of FAK.Therefore,the results of this study show that inflammation can promote the expression of FAK and ICAM-1 can regulate the expression of FAK through miR-15b-5p.