Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2

• Main Authors: Na Li, Shi-feng Liu, Kai Dong, Gui-chun Zhang, Jing Huang, Zhi-heng Wang, Tong-jian Wang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-10-01
• Series: Frontiers in Cellular and Infection Microbiology
• Subjects: miR-25; Helicobacter pylori; coronary heart disease; NF-κB; KLF2
• Online Access: https://www.frontiersin.org/article/10.3389/fcimb.2019.00366/full

Background: Increasing evidence has shown that Helicobacter pylori is associated with coronary heart disease (CHD); however, the underlying mechanism remains unclear.Methods: The expression of miR-25 and mRNAs was measured using qRT-PCR. Protein levels were detected using western blotting and exosomes were assessed with an electron microscope. The target gene of miR-25 was identified using the luciferase report system.Results:H. pylori infection increased the expression of miR-25 in gastric epithelial cells and was associated with increased levels of exosome-transmitted miR-25 in human peripheral blood. Mechanistic investigation showed the Kruppel-like factor 2 (KLF2) was a direct target of exosome-transmitted miR-25 in vascular endothelial cells. In addition, the miR-25/KLF2 axis regulated the NF-κB signaling pathway, resulting in increased expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1).Conclusion: Our findings suggest that the miR-25/KLF2 axis may be a potential therapeutic target for H. pylori-associated CHD. Furthermore, high levels of exosome-transmitted miR-25 in peripheral blood may pose a potential risk for CHD.