Master Autophagy Regulator Transcription Factor EB Regulates Cigarette Smoke-Induced Autophagy Impairment and Chronic Obstructive Pulmonary Disease–Emphysema Pathogenesis

Bodas, Manish; Patel, Neel; Silverberg, David; Walworth, Kyla; Vij, Neeraj

doi:10.1089/ars.2016.6842

Cited by 55 publications

(108 citation statements)

References 62 publications

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“…The studies of Hussain and Sandri (21) and Plant et al (22) demonstrated that autophagy can affect the bronchial-muscle function of patients with COPD. The pathophysiological mechanisms involved in COPD, including oxidative stress and inflammation, are associated with autophagy (14,(23)(24)(25). Therefore, autophagy serves a role in the pathogenesis of COPD.…”

Section: Discussionmentioning

confidence: 99%

Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease

et al. 2018

Mol Med Report

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Autophagy serves a role in the pathogenesis of chronic inflammatory diseases. The aim of the present study was to compare the autophagy levels in the peripheral blood mononuclear cells (PBMCs) of patients with chronic obstructive pulmonary disease (COPD) and healthy individuals and to assess the association between autophagy and the clinical parameters of COPD. Samples of peripheral blood from 20 patients with stable COPD and 20 healthy controls were collected. PBMCs were harvested using Ficoll density gradient centrifugation. Levels of the autophagy‑associated proteins ubiquitin‑binding protein p62 (p62), microtubule‑associated proteins 1A/1B light chain 3A (LC3I/II) and beclin‑1 in PBMCs were detected by western blotting. Enzyme‑linked immunosorbent assay kits were used to detect the serum concentrations of interleukin (IL)‑6, IL‑8 and tumor necrosis factor (TNF)‑α. Associations between the levels of autophagy and forced expiratory volume in 1 sec % predicted (FEV1%) and pro‑inflammatory factors were assessed. Western blotting demonstrated that the protein expression of p62 was decreased, but LC3II/I and beclin‑1 levels increased in patients with COPD compared with healthy controls. Serum levels of IL‑6, IL‑8 and TNF‑α were increased in patients with COPD. The extent of PBMC autophagy was negatively correlated with FEV1% predicted, but positively correlated with levels of pro‑inﬂammatory cytokines. The levels of autophagy in PBMCs in patients with COPD were increased and were negatively correlated with FEV1% predicted and positively correlated with circulating levels of pro‑inflammatory cytokines. Autophagy may serve a role as a biomarker of the severity of COPD or as a therapeutic target for treatment of COPD.

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Section: Discussionmentioning

confidence: 99%

Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease

et al. 2018

Mol Med Report

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“…Such an impairment of proteostasis with excessive activation of autophagy may lead to the accumulation of aggregated proteins and SQSTM1, leading to inefficient autophagy, epithelial cell dysfunction and death. 8,32,33 While smoke-induced autophagy in epithelial cells appears to promote airway inflammation (IL6 production and lymphocyte recruitment into the lung), 40,47,48 and impairment of mucociliary clearance function, 8,34 little is known about the role of autophagy in the inflammatory responses of infiltrating leukocytes into the lung in response to smoke. Autophagy is increased in AMs and neutrophils in response to smoke.…”

Section: Chronic Obstructive Pulmonary Disease Autophagy and Inflammmentioning

confidence: 99%

Autophagy and inflammation in chronic respiratory disease

et al. 2018

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Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases including chronic obstructive pulmonary disease, asthma and pulmonary fibrosis. Chronic inflammation in the lung may arise from a combination of genetic susceptibility and environmental influences, including exposure to microbes, particles from the atmosphere, irritants, pollutants, allergens, and toxic molecules. To this end, an immediate, strong, and highly regulated inflammatory defense mechanism is needed for the successful maintenance of homeostasis within the respiratory system. Macroautophagy/autophagy plays an essential role in the inflammatory response of the lung to infection and stress. At baseline, autophagy may be critical for inhibiting spontaneous pulmonary inflammation and fundamental for the response of pulmonary leukocytes to infection; however, when not regulated, persistent or inefficient autophagy may be detrimental to lung epithelial cells, promoting lung injury. This perspective will discuss the role of autophagy in driving and regulating inflammatory responses of the lung in chronic lung diseases with a focus on potential avenues for therapeutic targeting. Abbreviations AR allergic rhinitis AM alveolar macrophage ATG autophagy-related CF cystic fibrosis CFTR cystic fibrosis transmembrane conductance regulator COPD chronic obstructive pulmonary disease CS cigarette smoke CSE cigarette smoke extract DC dendritic cell IH intermittent hypoxia IPF idiopathic pulmonary fibrosis ILD interstitial lung disease MAP1LC3B microtubule associated protein 1 light chain 3 beta MTB Mycobacterium tuberculosis MTOR mechanistic target of rapamycin kinase NET neutrophil extracellular traps OSA obstructive sleep apnea PAH pulmonary arterial hypertension PH pulmonary hypertension ROS reactive oxygen species TGFB1 transforming growth factor beta 1 TNF tumor necrosis factor.

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“…Epigenetic modifications, including changes in histone deacetylase 2 activity, have been identified in all three conditions [49][50][51]. A loss of proteostasis and autophagy has been associated with emphysema in COPD [52] and also contribute to T2D [53] and atherosclerosis progression [54].…”

Section: Theme 1: Accelerated Ageing In Multimorbiditymentioning

confidence: 99%

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

2020

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Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.

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Master Autophagy Regulator Transcription Factor EB Regulates Cigarette Smoke-Induced Autophagy Impairment and Chronic Obstructive Pulmonary Disease–Emphysema Pathogenesis

Abstract: TFEB-inducing drug(s) can control CS-induced TFEB/autophagy-impairment and COPD-emphysema pathogenesis. Antioxid. Redox Signal. 27, 150-167.

Cited by 55 publications

References 62 publications

Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease

Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease

Autophagy and inflammation in chronic respiratory disease

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

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