Research Paper Volume 12, Issue 2 pp 1141—1158
MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway
- 1 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China
received: October 1, 2019 ; accepted: December 25, 2019 ; published: January 18, 2020 ;https://doi.org/10.18632/aging.102672
How to Cite
Copyright © 2020 Wang 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.
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.
BALF: bronchoalveolar lavage fluid; C1QTNF6: complement C1q tumor necrosis factor-related protein 6; COPD: chronic obstructive pulmonary diseases; DALYs: disability-adjusted life-years; ELISA: enzyme-linked immunosorbent assay; HBECs: human bronchial epithelial cells; MiRNAs: microRNAs; PAHs: polycyclic aromatic hydrocarbons; PCB: polychlorinated biphenyl; PM: particulate matter; RIPA: radioimmunoprecipitation assay buffer; PMSF: phenylmethanesulfonyl fluoride; PVDF: polyvinylidene difluoride.