MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway

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 factorrelated 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.

Non-Coding RNAs in COVID-19: Emerging Insights and Current Questions

“…However, miR-29-3p was thought to promote IL-8 and other cytokine expression in a mouse respiratory disease model [41]. However, miR-31 is also associated with TNS1 downregulation, an enhancer of immune infiltration [23].…”

“…The study does not explore the contextual mechanism of these miRNAs, but they may be further evidence of the unique infection and CSS-related inflammation that is severe COVID-19, given that existing literature implicates these two miRNAs in both pro-inflammatory and anti-inflammatory function, depending on disease. For instance, in a model of particulate matter-induced respiratory disease (therefore not infection-related), miR-29-3p was in fact found to promote IL-8 and other pro-inflammatory cytokine expression [ 41 ], despite being inversely correlated with IL-8 in COVID-19 [ 37 ]. Conversely, in an infection event, another study linked miR-29b-3p upregulation with reduced MAPK activation and NF-κB signalling after LPS stimulation in neonatal rat cardiomyocytes, reducing inflammatory damage in this model of sepsis-induced cardiac arrest [ 40 ].…”

“…▪ However, miR-29-3p was thought to promote IL-8 and other cytokine expression in a mouse respiratory disease model [ 41 ].…”

C1QTNF6 is a Prognostic Biomarker and Related to Immune Infiltration and Drug Sensitivity: A Pan-Cancer Analysis

“…Complement C1q Tumor Necrosis factor-related Protein 6 ( C1QTNF6 ) is an inflammation-related gene, which has been preliminarily described to be related to the biological characteristics of tumors ( Wang et al, 2020 ). Zhang et al found that C1QTNF6 regulates proliferation and apoptosis of non-small cell lung cancer (NSCLC) ( Zhang and Feng, 2021 ).…”

Silencing microRNA‑29b‑3p expression protects human trabecular meshwork cells against oxidative injury via upregulation of RNF138 to activate the ERK pathway

“…For example, miR-29b-3p expression is upregulated in patients with congenital heart disease and miR-29b-3p silencing promotes cardiomyocyte proliferation via targeting NOTCH2 ( 17 ). miR-29b-3p contributes to the inflammatory response of human bronchial epithelial cells stimulated by particulate matter by suppressing the AMPK pathway ( 18 ). miR-29b-3p promotes the apoptosis of retinal microvascular endothelial cells via downregulating sirtuin-1 in an in vitro model of diabetic retinopathy ( 19 ).…”