Ze Zheng1, Xuebao Zhang1, Jiemei Wang1, Aditya Dandekar2, Hyunbae Kim1, Yining Qiu1, Xiaohua Xu3, Yuqi Cui4, Aixia Wang5, Lung Chi Chen6, Sanjay Rajagopalan4, Qinghua Sun5, Kezhong Zhang7. 1. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA. 2. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA. 3. Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA. 4. Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH 43210, USA. 5. 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. 6. Department of Environmental Medicine, New York University, Tuxedo, NY 10987, USA. 7. 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.
Abstract
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.
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.
Authors: Thomas Kampfrath; Andrei Maiseyeu; Zhekang Ying; Zubair Shah; Jeffrey A Deiuliis; Xiaohua Xu; Nisharahmed Kherada; Robert D Brook; Kongara M Reddy; Nitin P Padture; Sampath Parthasarathy; Lung Chi Chen; Susan Moffatt-Bruce; Qinghua Sun; Henning Morawietz; Sanjay Rajagopalan Journal: Circ Res Date: 2011-01-27 Impact factor: 17.367
Authors: Samuele De Minicis; Ekihiro Seki; Yong-Han Paik; Christoph H Osterreicher; Yuzo Kodama; Johannes Kluwe; Luciano Torozzi; Katsumi Miyai; Antonio Benedetti; Robert F Schwabe; David A Brenner Journal: Hepatology Date: 2010-10 Impact factor: 17.425
Authors: Hui-Hui Tan; M Isabel Fiel; Qinghua Sun; Jinsheng Guo; Ronald E Gordon; Lung-Chi Chen; Scott L Friedman; Joseph A Odin; Jorge Allina Journal: J Immunotoxicol Date: 2009-12 Impact factor: 3.000
Authors: John F Pearson; Chethan Bachireddy; Sangameswaran Shyamprasad; Allison B Goldfine; John S Brownstein Journal: Diabetes Care Date: 2010-07-13 Impact factor: 19.112
Authors: Fen Yin; Rajat Gupta; Laurent Vergnes; Will S Driscoll; Jerry Ricks; Gajalakshmi Ramanathan; James A Stewart; Diana M Shih; Kym F Faull; Simon W Beaven; Aldons J Lusis; Karen Reue; Michael E Rosenfeld; Jesús A Araujo Journal: Arterioscler Thromb Vasc Biol Date: 2019-07-25 Impact factor: 8.311
Authors: Trang VoPham; Kimberly A Bertrand; Rulla M Tamimi; Francine Laden; Jaime E Hart Journal: Cancer Causes Control Date: 2018-04-25 Impact factor: 2.506
Authors: Xiangmeng Chen; Teng Ma; Rowena Yip; Ponni V Perumalswami; Andrea D Branch; Sara Lewis; Michael Crane; David F Yankelevitz; Claudia I Henschke Journal: Clin Imaging Date: 2019-12-12 Impact factor: 1.605
Authors: Yijing Feng; Miranda R Jones; JiYoon B Ahn; Jacqueline M Garonzik-Wang; Dorry L Segev; Mara McAdams-DeMarco Journal: Am J Transplant Date: 2021-05-20 Impact factor: 9.369