Zn2+ loading as a critical contributor to the circ_0008553-mediated oxidative stress and inflammation in response to PM2.5 exposures
2023
Wang, Jingzhou | Jia, Jianbo | Wang, Dujia | Pan, Xiujiao | Xiong, Haiyan | Li, Chengjun | Jiang, Yiguo | Yan, Bing
Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of ≤ 2.5 µm (PM₂.₅), and a critical trigger of most PM₂.₅ exposure-associated diseases. However, the key molecular events regulating the PM₂.₅-induced airway inflammation are yet to be elucidated. Considering the critical role of circular RNAs (circRNAs) in regulating inflammation, we predicted 11 circRNAs that may be involved in the PM₂.₅-induced airway inflammation using three previously reported miRNAs through the starBase website. A novel circRNA circ_0008553 was identified to be responsible for the PM₂.₅-activated inflammatory response in human bronchial epithelial cells (16HBE) via inducing oxidative stress. Using a combinatorial model PM₂.₅ library, we found that the synergistic effect of the insoluble core and loaded Zn²⁺ ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM₂.₅ exposures. Our findings provided new insight into the intervention of PM₂.₅-induced adverse outcomes.
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