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Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models

  • Ze Zheng
    Affiliations
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Xuebao Zhang
    Affiliations
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Jiemei Wang
    Affiliations
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Aditya Dandekar
    Affiliations
    Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Hyunbae Kim
    Affiliations
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Yining Qiu
    Affiliations
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Xiaohua Xu
    Affiliations
    Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA
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  • Yuqi Cui
    Affiliations
    Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA
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  • Aixia Wang
    Affiliations
    Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA

    Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA
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  • Lung Chi Chen
    Affiliations
    Department of Environmental Medicine, New York University, Tuxedo, NY 10987, USA
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  • Author Footnotes
    † Current address: Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
    Sanjay Rajagopalan
    Footnotes
    † Current address: Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
    Affiliations
    Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA
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  • Qinghua Sun
    Affiliations
    Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA

    Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA
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  • Kezhong Zhang
    Correspondence
    Corresponding author. Address: 540 E. Canfield Avenue, Detroit, MI 48201, USA. Tel.: +1 313 577 2669; fax: +1 313 577 5218.
    Affiliations
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA

    Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA
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  • Author Footnotes
    † Current address: Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

      Background & Aims

      Hepatic fibrosis, featured by the accumulation of excessive extracellular matrix in liver tissue, is associated with metabolic disease and cancer. Inhalation exposure to airborne particulate matter in fine ranges (PM2.5) correlates with pulmonary dysfunction, cardiovascular disease, and metabolic syndrome. In this study, we investigated the effect and mechanism of PM2.5 exposure on hepatic fibrogenesis.

      Methods

      Both inhalation exposure of mice and in vitro exposure of specialized cells to PM2.5 were performed to elucidate the effect of PM2.5 exposure on hepatic fibrosis. Histological examinations, gene expression analyses, and genetic animal models were utilized to determine the effect and mechanism by which PM2.5 exposure promotes hepatic fibrosis.

      Results

      Inhalation exposure to concentrated ambient PM2.5 induces hepatic fibrosis in mice under the normal chow or high-fat diet. Mice after PM2.5 exposure displayed increased expression of collagens in liver tissues. Exposure to PM2.5 led to activation of the transforming growth factor β-SMAD3 signaling, suppression of peroxisome proliferator-activated receptor γ, and expression of collagens in hepatic stellate cells. NADPH oxidase plays a critical role in PM2.5-induced liver fibrogenesis.

      Conclusions

      Exposure to PM2.5 exerts discernible effects on promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM2.5 exposure on promoting hepatic fibrosis.

      Graphical abstract

      Abbreviations:

      PM (ambient particulate matter), PM2.5 (PM with aerodynamic diameter less than 2.5μm), FA (filtered air), OASIS (Ohio’s Air Pollution Exposure System for the Interrogation of Systemic Effects), PPAR (peroxisome proliferator-activated receptor), TGFβ (transforming growth factor β), HSC (hepatic stellate cells), p47phox (Neutrophil cytosolic factor 1), NOX (NADPH peroxidase), ROS (reactive oxygen species)

      Keywords

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