Abstract
Inflammatory responses are considered to be the critical mechanism underlying particulate matter (PM)-induced development and exacerbation of chronic respiratory diseases. MiR-29b-3p has been found to participate in various biological processes, but its role in PM-induced inflammatory responses was previously unknown. Here, we constructed a miRNA PCR array to find that miR-29b-3p was the most highly expressed in human bronchial epithelial cells (HBECs) exposed to PM. MiR-29b-3p promoted PM-induced pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) expression via inhibiting the AMPK signaling pathway in HBECs. RNA sequencing and luciferase reporter assay identified that miR-29b-3p targeted complement C1q tumor necrosis factor-related protein 6 (C1QTNF6), a protein that protected from PM-induced inflammatory responses via activating the AMPK signaling pathway. In vivo, miR-29b-3p antagomirs delivered via the tail vein prior to PM exposure significantly counteracted PM-induced miR-29b-3p upregulation and C1QTNF6 downregulation in lung tissues. Furthermore, miR-29b-3p inhibition alleviated inflammatory cells infiltration and pro-inflammatory cytokines secretion in the lung of PM-exposed mice. These findings firstly revealed that miR-29b-3p acted as a novel modulator of PM-induced inflammatory responses by targeting the C1QTNF6/AMPK signaling pathway, which contributes to a better understanding of the biological mechanisms underlying adverse PM-induced respiratory health effects.
Highlights
Ambient particulate matter (PM) is the key component of air pollution, which is a great threat to global health, especially in developing countries
We found that miR-29b-3p was the most highly upregulated in the PM-exposed human bronchial epithelial cells (HBECs) (Figure 1A)
Based on both in vivo and in vitro PM exposure models, we showed that PM exposure promoted miR-29b-3p expression in airway epithelial cells and macrophages, and miR-29b3p inhibition significantly attenuated PM-induced pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) and inflammatory cell infiltration
Summary
Ambient particulate matter (PM) is the key component of air pollution, which is a great threat to global health, especially in developing countries. The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) showed that PM exposure caused 4.58 million deaths and 143 million disability-adjusted life-years (DALYs) across the world in 2017 [1]. Inflammatory responses are considered to be the main biological mechanism underlying the adverse PM-induced respiratory health effects. A panel study reported that fine PM exposure elevated the levels of several pro-inflammatory cytokines in the blood of healthy young adults with no history of smoking [3]. Numerous studies have shown that PM exposure promotes the expression of pro-inflammatory cytokines in human bronchial epithelial cells (HBECs), alveolar epithelial cells, and macrophages [4, 5]. Oxidative stress and several signaling pathways have been shown to regulate PM-induced inflammatory responses [6]. Proteins (amphiregulin and osteopontin) were found to participate in regulating www.aging-us.com
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