Exosomes derived from ITGB1 modified Telocytes alleviates LPS-induced inflammation and oxidative stress through YAP1/ROS axis

Heliyon. 2024 Mar 8;10(5):e27086. doi: 10.1016/j.heliyon.2024.e27086. eCollection 2024 Mar 15.

Abstract

Aims: Previous studies have demonstrated a significant upregulation of Integrin Beta 1 (ITGB1) in Telocytes. This study aims to explore the roles and underlying mechanisms of ITGB1 in inflammation and oxidative stress following Lipo-polysaccharide (LPS) administration in Telocytes.

Methods: We observed an increase in reactive oxygen species (ROS) production, accompanied by a reduction in ITGB1 levels post-LPS treatment.

Results: Notably, inhibiting ROS synthesis markedly reduced LPS-induced ITGB1 expression. Additionally, ectopic ITGB1 expression mitigated LPS-induced inflammation and oxidative stress, evident through decreased levels of pro-inflammatory markers such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-6, and Monocyte Chemoattractant Protein (MCP)-1. Depletion of endothelial Yes-Associated Protein 1 (YAP1) notably diminished the levels of inflammatory markers and ROS production. Furthermore, exosomes secreted by ITGB1-modified Telocytes promoted Human Umbilical Vein Endothelial Cells (HUVECs) proliferation and inhibited apoptosis. In vivo experiments revealed that exosomes from ITGB1-modified Telocytes modulated functional and structural changes, as well as inflammatory responses in Acute Lung Injury (ALI).

Conclusion: These findings highlight the critical role of the YAP1/ROS axis in LPS-induced Telocyte injuries, underlining the therapeutic potential of targeting ITGB1 for mitigating inflammation and oxidative stress in these cells.

Keywords: Exosomes; ITGB1; Inflammation; LPS; Oxidative stress; ROS; YAP1.