title: Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Jiemei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Dandekar
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Hyunbae
authors.initials: H
authors.lastname: Kim
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Yining
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Environmental Medicine, New York University, Tuxedo, NY 10987, USA.
authors.forename: Lung Chi
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.affiliation: 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.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.affiliation: 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. Electronic address: kzhang@med.wayne.edu.
authors.forename: Kezhong
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D055166:Hepatic Stellate Cells / Q000378:metabolism; D019570:Inhalation Exposure; D007728:Kupffer Cells / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D052638:Particulate Matter; D016212:Transforming Growth Factor beta; D003094:Collagen; D019255:NADPH Oxidases
keywords: Air pollution; Hepatic fibrosis; PM(2.5)