Trichloroethylene-induced downregulation of miR-199b-5p contributes to SET-mediated apoptosis in hepatocytes

Ren, Xiaohu; Chen, Zhihong; Ruan, Jiawen; Zhong, Jiacheng; Deng, Rongxia; Liu, Wei; Huang, Xinfeng; Yang, Xifei; Liu, Yungang; Li, Jianjun

doi:10.1007/s10565-019-09479-3

Cited by 14 publications

(8 citation statements)

References 28 publications

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“…Occupational exposure to TCE is known to be associated with differential expression of certain serum microRNAs [ 19 , 27 ]. In this study, we used microRNA microarray technology to screen and identify 69 significantly expressed serum microRNAs.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of miR-21-5p and miR-339-5p associate with occupational trichloroethylene hypersensitivity syndrome

Liu

Zheng

Ren

et al. 2021

J Occup Med Toxicol

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Background Trichloroethylene (TCE) hypersensitivity syndrome (THS) is a dose-independent and potentially life-threatening disease. In this study, we sought to identify THS-related miRNAs and evaluate its potential clinical value. Methods Serum samples of five patients and five matched TCE contacts were used for screening differential miRNAs. Another 34 patients and 34 matched TCE contacts were used for verifying significantly differential miRNAs with SYBR™ Green PCR and MGB PCR. The diagnostic model based on these miRNAs was established via the support vector machine (SVM) algorithm. Correlation between differential miRNAs and liver function was analyzed via the Spearman correlation test. Results A total of 69 miRNAs was found to be differentially expressed. MiR-21-5p and miR-339-5p were verified to have significant higher expressions in patients. The sensitivity, specificity and accuracy of disease model were 100, 75 and 86%, respectively. The two miRNAs showed significant correlations with liver function. Conclusion These findings suggested that miRNAs profiles in serum of THS patients had changed significantly, and miR-21-5p and miR-339-5p were associated with THS.

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Section: Discussionmentioning

confidence: 99%

Serum levels of miR-21-5p and miR-339-5p associate with occupational trichloroethylene hypersensitivity syndrome

Liu

Zheng

Ren

et al. 2021

J Occup Med Toxicol

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“…TCE enters the body through bioaccumulation and can exert toxic effects through oxidative metabolism (Wood et al 2015). Damage to the skin and organs of humans and other organisms has been widely con rmed (Horzmann et al 2020;Lai et al 2021), with the liver as the most common organ involved (Zhao et al 2020;Zhang et al 2017;Ren et al 2019). Studies have shown that TCE and its metabolites can cause epigenetic changes, altering immune function and promoting liver in ammation (Blossom et al 2018;Ordaz et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Trichloroethylene induced hepatic injury via M1 macrophage polarization through KDM4A associated with the Wnt/β-catenin pathway in vitro and in vivo

Zhang,

Huang,

Ding

et al. 2023

Preprint

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Background & Aims: Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the liversof TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. Methods: In the study, BALB/c mice were treated with TCE by drinking water. The mice were randomly divided into 4 groups: 2.5 milligrams per milliliter (mg/mL) TCE dose group (n=24) and 5.0 mg/mL TCE dose group (n=24), TCE used 1% DMSO to aid solubilization, the vehicle control group (drinking water containing 1% DMSO) (n=24), and the blank control group (fed with normal drinking water) (n=24). Drinking water was replaced every 24 h to ensure the stability of the TCE concentration. The mice were sacrificed at four time points of 2, 4, 8 and 12 weeks, and biological sample material were taken aseptically. Results: TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines (e.g., TNF-α andIL-1β). Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 andincreased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to β-catenin activation, a signal critical for the proinflammatoryactivation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in β-catenin expression andprevented TCE-induced M1 polarization and the expression of the proinflammatory cytokines TNF-α and IL-1β. These results suggest that the association of KDM4A and Wnt/β-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Conclusion: Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.

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“…However, response of hepatic cells to TCE-induced DNA damage still remains uncharacterized. In previous studies, we identi ed the histone chaperon, SET as a key mediator for TCE-induced liver cell apoptosis (Yang et al 2012) and explored related regulatory mechanisms (Ren et al 2019;Ruan et al 2018). Additionally, we also found that TCE induces abnormal acetylation in histones via mediation of SET (Li et al 2021;Deng et al 2017).…”

Section: Introductionmentioning

confidence: 99%

SET-mediated epigenetic dysregulation of p53 impairs trichloroethylene-induced DNA damage response

ren,

Ruan,

Lan

et al. 2023

Toxicology Letters

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Trichloroethylene-induced downregulation of miR-199b-5p contributes to SET-mediated apoptosis in hepatocytes

Cited by 14 publications

References 28 publications

Serum levels of miR-21-5p and miR-339-5p associate with occupational trichloroethylene hypersensitivity syndrome

Serum levels of miR-21-5p and miR-339-5p associate with occupational trichloroethylene hypersensitivity syndrome

Trichloroethylene induced hepatic injury via M1 macrophage polarization through KDM4A associated with the Wnt/β-catenin pathway in vitro and in vivo

SET-mediated epigenetic dysregulation of p53 impairs trichloroethylene-induced DNA damage response

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