PM2.5-induced alteration of DNA methylation and RNA-transcription are associated with inflammatory response and lung injury

Shi, Yanfeng; Zhao, Tong; Yang, Xiaozhe; Sun, Baiyang; Li, Yang; Duan, Junchao; Sun, Zhiwei

doi:10.1016/j.scitotenv.2018.09.085

Cited by 72 publications

(33 citation statements)

References 90 publications

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“…It is well known that the lung is the direct target organ for inhaling damage caused by PM2.5. Accumulating data suggest that the increasing PM2.5 is associated with the development of various lung diseases including asthma, lung injury, and pulmonary fibrosis 10,37,38 . PM2.5 mainly contains 16 kinds of polycyclic aromatic hydrocarbons (PAHs) and metals, and excessive production of ROS is one of the key factors for PM2.5-induced cell damage.…”

Section: Discussionmentioning

confidence: 99%

Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis

Yang

Liu

et al. 2020

Cell Death Dis

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Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by chronic non-specific inflammation of the interstitial lung and extensive deposition of collagen fibers leading to destruction of lung function. Studies have demonstrated that exposure to fine particulate matter (PM2.5) increases the risk of IPF. In order to recover from PM2.5-induced lung injury, alveolar epithelial cells need to be repaired and regenerated to maintain lung function. Type 2 alveolar epithelial cells (AEC2) are stem cells in the adult lung that contribute to the lung repair process through complex signaling. Our previous studies demonstrated that RAB6, a RAS family member lowly expressed in lung cancer, inhibited lung cancer stem cell self-renewal, but it is unclear whether or not and how RAB6 may regulate AEC2 cell proliferation and self-renewal in PM2.5-induced pulmonary fibrosis. Here, we demonstrated that knockout of RAB6 inhibited pulmonary fibrosis, oxidative stress, and AEC2 cell death in PM2.5-injured mice. In addition, knockout of RAB6 decreased Dickkopf 1(DKK1) autocrine and activated proliferation, self-renewal, and wnt/β-catenin signaling of PM2.5-injured AEC2 cells. RAB6 overexpression increased DKK1 autocrine and inhibited proliferation, self-renewal and wnt/β-catenin signaling in AEC2 cells in vitro. Furthermore, DKK1 inhibitors promoted proliferation, self-renewal and wnt/β-catenin signaling of RAB6 overexpressing AEC2 cells, and attenuated PM2.5-induced pulmonary fibrosis in mice. These data establish RAB6 as a regulator of DKK1 autocrine and wnt/β-catenin signal that serves to regulate AEC2 cell proliferation and self-renewal, and suggest a mechanism that RAB6 disruption may promote AEC2 cell proliferation and self-renewal to enhance lung repair following PM2.5 injury.

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Section: Discussionmentioning

confidence: 99%

Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis

Yang

Liu

et al. 2020

Cell Death Dis

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“…). We further know that exposure to PM2.5 is associated with DNA methylation, which may in turn affect lung function or/ and brain health negatively(Shi et al 2019). Additionally, we found evidence for the relevance of the indirect route over the lung in cognitive impairments by fine particulate matter.…”

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confidence: 99%

Long-Term Exposure to Fine Particulate Matter, Lung Function and Cognitive Performance: A Prospective Dutch Cohort Study on the Underlying Routes

Aretz

Janssen

Vonk

et al. 2020

Preprint

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Background Exposure to fine particulate matter and black carbon is related to cognitive impairment and poor lung function, but less is known about the routes taken by different types of air pollutants to affect cognition. Objectives We tested two possible routes of fine particulate matter (PM2.5) and black carbon (BC) in impairing cognition, and evaluated their importance: a direct route over the olfactory nerve or the blood stream, and an indirect route over the lung. Methods We used longitudinal observational data for 31232 people aged 18+ from 2006 to 2015 from the Dutch Lifelines cohort study. By linking current and past home addresses to air pollution exposure data from ELAPSE, long-term average exposure (≤ ten years) to PM2.5 and BC was calculated. Lung function was assessed by spirometry and Global Initiative (GLI) z-scores of forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were calculated. Cognitive performance was measured by cognitive processing time (CPT) assessed by the Cogstate Brief Battery. Linear structural equation modeling was performed to test the direct/indirect associations. Results Higher exposure to PM2.5 but not BC was directly related to higher CPT and thus slower cognitive processing speed [18.33 (×10-3) SD above the mean (95% CI: 6.84, 29.81)]. The direct association of PM2.5 constituted more than 97% of the total effect. Mediation by lung function was low for PM2.5 with a mediated proportion of 1.78% (FEV1) and 2.62% (FVC), but higher for BC (28.49% and 46.22% respectively). Discussion Our results emphasize the importance of the lung acting as a mediator in the relationship between both exposure to PM2.5 and BC, and cognitive performance. However, higher exposure to PM2.5 was mainly directly associated with worse cognitive performance, which emphasizes the health-relevance of fine particles due to their ability to reach vital organs directly.

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“…The gene expression of inflammatory factors usually was regulated by DNA methylation [47][48][49]. Bacterial pathogens have an ability to directly influence the DNA methylation status of a host and then cause the development of inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

Sun

Dong

et al. 2020

Toxins

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Mastitis is usually caused by a variety of pathogenic bacteria that include both Gram-positive and Gram-negative bacteria. Lipopolysaccharide (LPS) is the pathogen-associated molecular pattern (PAMP) of Gram-negative bacteria, and peptidoglycan (PGN) and lipoteichoic acid (LTA) are those of Gram-positive bacteria. The effects of LPS, PGN and/or LTA on inflammatory response and lactation in bovine mammary epithelial cells (BMECs) are well studied, but the epigenetic mechanisms of their effects received less attention. Furthermore, since the three PAMPs are often simultaneously present in the udder of cows with mastitis, it has implications in practice to study their additive effects. The results show that co-stimulation of bovine mammary epithelial cells with PGN, LTA, and LPS induced a higher number of differentially expressed genes (DEGs) and greater expressions of inflammatory factors including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand (CXCL)1, and CXCL6. In addition, co-stimulation further increased DNA hypomethylation compared with sole LPS stimulation. Co-stimulation greatly decreased casein expression but did not further decrease histone acetylation levels and affect the activity of histone acetyltransferase (HAT) and histone deacetylase (HDAC), compared with sole LPS stimulation. Collectively, this study demonstrated that PGN, LTA, and LPS had an additive effect on inducing transcriptome changes and inflammatory responses in BMECs, probably through inducing a greater decrease in DNA methylation. Co-stimulation with PGN, LTA, and LPS decreased casein expression to a greater degree, but it might not be linked to histone acetylation and HAT and HDAC activity.

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PM2.5-induced alteration of DNA methylation and RNA-transcription are associated with inflammatory response and lung injury

Cited by 72 publications

References 90 publications

Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis

Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis

Long-Term Exposure to Fine Particulate Matter, Lung Function and Cognitive Performance: A Prospective Dutch Cohort Study on the Underlying Routes

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

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