Research Paper Volume 14, Issue 16 pp 6796—6808
MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1
- 1 Department of Rheumatic Immunology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- 2 Department of Respiratory Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- 3 Intensive Care Unit, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, China
- 4 Office of Academic Research, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- 5 College of Pharmacy, The Hebei Medical University, Shijiazhuang, Hebei, China
- 6 Department of Respiratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
Received: December 28, 2021 Accepted: August 9, 2022 Published: August 29, 2022
https://doi.org/10.18632/aging.204254How to Cite
Copyright: © 2022 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: To explore the roles of macrophages’ miR-217-5p in the process of PM2.5 induced acute lung injury.
Methods: GEO database and KEGG pathway enrichment analysis as well as GSEA were used to predicted the miRNA and associated target signals. And then mice and RAW246.7 macrophages treated with PM2.5 to imitate PM2.5 induced acute lung injury environment and then transfected with miR-217-5p NC or miR-217-5p mimic. The levels of inflammatory factors TNF-α and anti-inflammatory factor IL-10 of mice serum were tested by ELISA. And the pathological changes and ROS level of mouse lung tissues were stained by HE and DHE staining. The proteins expression of phosphorylated-STAT1, total-STAT1, TNF-α, IFN-γ as well as p47, gp91, NOX4 in mice or RAW264.7 cells were tested by western blot or immunofluorescence of RAW264.7 cell slides.
Results: The results of bioinformatics analysis indicated the miR-217 as well as STAT1 were involved PM2.5 associated lung injury. After exposure to PM2.5, the decreased levels of serum TNF-α but not IL-10, consistent with reduced macrophages’ accumulation as well as decreased ROS levels in lung tissues in miR-217-5p mimic group vs miR-217-5p NC group mice, and moreover, the protein expression levels of phosphorylated--STAT1, total-STAT1, TNF-α, IFN-γ, p47, gp91 and NOX4 in mouse lung tissues and RTAW246.7 macrophages cells were all significantly reduced with miR-217-5p mimic administration. The above phenomena were reversed by specific STAT1-inhibitor HY-N8107.
Conclusions: miR-217-5p suppressed the activated STAT1-signal induced inflammation and oxidative stress trigged by PM2.5 in macrophages and resulted in the decreased lung injure caused by PM2.5.