Global DNA methylation and PTEN hypermethylation alterations in lung tissues from human silicosis

Zhang, Xianan; Jia, Xiaowei; Mei, Liangying; Zheng, Min; Chen, Yu; Ye, Meng

doi:10.21037/jtd.2016.07.21

Cited by 20 publications

(27 citation statements)

References 37 publications

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“…When respirable CS particles are inhaled, their entry into alveoli induces oxidative stress through the formation of reactive oxygen (ROS) and nitrogen species due to the generation of siloxil radicals after crystalline-silica fracturing [8]. Therefore, it leads to extensive fibroblast proliferation and deposition of extracellular matrix (ECM) with the lungs and further triggers cytotoxicity, oxidative stress, pulmonary inflammation, and eventually silicosis [9]. In the meantime, the progression of lung fibrosis is accompanied with infiltration of inflammatory cells including eosinophils, neutrophils, and macrophages.…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine tiherapeutically protects against pulmonary fibrosis in a mouse model of silicosis

et al. 2019

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Silicosis is a lethal pneumoconiosis disease characterized by chronic lung inflammation and fibrosis. The present study was to explore the effect of against crystalline silica (CS)-induced pulmonary fibrosis. A total of 138 wild-type C57BL/6J mice were divided into control and experimental groups, and killed on month 0, 1, 2, 3, 4, and 5. Different doses of N-acetylcysteine (NAC) were gavaged to the mice after CS instillation to observe the effect of NAC on CS induced pulmonary fibrosis and inflammation. The pulmonary injury was evaluated with Hematoxylin and eosin/Masson staining. Reactive oxygen species level was analyzed by DCFH-DA labeling. Commercial ELISA kits were used to determine antioxidant activity (T-AOC, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) and cytokines (TNF-α, IL-1β, IL-4, and IL-6). The expression of oxidising enzymes (NOX2, iNOS, SOD2, and XO) were detected by real time PCR. Immunohistochemistry (IHC) staining was performed to examine epithelial-mesenchymal transition-related markers. The mice treated with NAC presented markedly reduced CS-induced pulmonary injury and ameliorated CS-induced pulmonary fibrosis and inflammation. The level of malondialdehyde was reduced, while the activities of GSH-PX, SOD, and T-AOC were markedly enhanced by NAC. We also found the down-regulation of oxidising enzymes (NOX2, iNOS, SOD2, and XO) after NAC treatment. Moreover, E-cadherin expression was increased while vimentin and Cytochrome C expressions were decreased by NAC. These encouraging findings suggest that NAC exerts pulmonary protective effects in CS-induced pulmonary fibrosis and might be considered as a promising agent for the treatment of silicosis.

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Section: Introductionmentioning

confidence: 99%

N-acetylcysteine tiherapeutically protects against pulmonary fibrosis in a mouse model of silicosis

et al. 2019

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“…Additionally, epigenetic modifications (such as DNA methylation and histone acetylation) may also regulate the expression of PTEN. PTEN loss caused by aberrant hypermethylation of the DNA promoter region has been identified in various malignant and benign (nontumor) diseases (Mueller et al, 2012;Zhang et al, 2016;Geybels et al, 2017). Moreover, histone acetylation induced by the interaction of transcription factor SAL-like protein 4 and NuRD (a histone deacetylase repressor complex) at the promoter region can regulate PTEN transcription (Lu et al, 2009).…”

Section: Biological Functions and Regulation Of Ptenmentioning

confidence: 99%

Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

Zhang

Hao

et al. 2021

Front. Physiol.

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The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.

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“…Asbestos fibers and silica particles can induce high level of ROS production by the Fenton's reaction that is initiated by the iron at their surfaces [45,46] as well as by their ability to cause incomplete phagocytosis and inflammation [47]. Increased production of ROS [48], base oxidation damage [49], single strand breaks (SSBs) [49], DSBs [50], as well as gain of aberrant DNA methylation at the promoter of the tumor suppressor genes O 6 -methylguanine-DNA methyltransferase (MGMT), p16, RASSF1A, and PTEN [51] [52] [53], and reduced expression of tumor suppressing miRNAs, miRNA-181 and miRNA-29 [54] are caused by asbestos and/or silica particles.…”

Section: Chronic Inflammation Caused By Non-infectious Agents and Diseasesmentioning

confidence: 99%

The emerging role of epigenetic modifiers in repair of DNA damage associated with chronic inflammatory diseases

Ding

Maiuri

O’Hagan

2019

Mutation Research/Reviews in Mutation Research

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At sites of chronic inflammation epithelial cells are exposed to high levels of reactive oxygen species (ROS), which can contribute to the initiation and development of many different human cancers. Aberrant epigenetic alterations that cause transcriptional silencing of tumor suppressor genes are also implicated in many diseases associated with inflammation, including cancer. However, it is not clear how altered epigenetic gene silencing is initiated during chronic inflammation. The high level of ROS at sites of inflammation is known to induce oxidative DNA damage in surrounding epithelial cells. Furthermore, DNA damage is known to trigger several responses, including recruitment of DNA repair proteins, transcriptional repression, chromatin modifications and other cell signaling events. Recruitment of epigenetic modifiers to chromatin in response to DNA damage results in transient covalent modifications to chromatin such as histone ubiquitination, acetylation and methylation and DNA methylation. DNA damage also alters noncoding RNA expression. All of these alterations have the potential to alter gene expression at sites of damage. Typically, these modifications and gene transcription are restored back to normal once the repair of the DNA damage is completed. However, chronic inflammation may induce sustained DNA damage and DNA damage responses that result in these transient covalent chromatin modifications becoming mitotically stable epigenetic alterations. Understanding how epigenetic alterations are initiated during chronic inflammation will allow us to develop pharmaceutical strategies to prevent or treat chronic inflammation-induced cancer. This review will focus on types of DNA damage and epigenetic alterations associated with chronic inflammatory diseases, the types of DNA damage and transient covalent chromatin modifications induced by inflammation and oxidative DNA damage and how these modifications may result in epigenetic alterations.

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Global DNA methylation and PTEN hypermethylation alterations in lung tissues from human silicosis

Cited by 20 publications

References 37 publications

N-acetylcysteine tiherapeutically protects against pulmonary fibrosis in a mouse model of silicosis

N-acetylcysteine tiherapeutically protects against pulmonary fibrosis in a mouse model of silicosis

Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

The emerging role of epigenetic modifiers in repair of DNA damage associated with chronic inflammatory diseases

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