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Particulate Matter Exposure Promotes a Profibrotic Phenotype in Pulmonary Fibroblasts
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A2821 - Particulate Matter Exposure Promotes a Profibrotic Phenotype in Pulmonary Fibroblasts
Author Block: N. Craig, P. Tripathi, A. Scruggs, S. K. Huang; Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States.
Rationale: Idiopathic pulmonary fibrosis (IPF) is traditionally considered a respiratory disease of unknown cause, but many investigators have suspected certain environmental exposures, such as wood particulates and metal dust, to be important risk factors. Recent studies have shown that exposure to ambient air pollution, including particulate matter (PM2.5), has been associated with more rapid progression of IPF. Despite this epidemiological evidence, the role that air pollution and PM2.5 have in the pathogenesis of IPF remains understudied. As fibroblasts are the major effector cell of fibrosis, we sought to examine the direct effect of PM2.5 on the functions and actions of human lung fibroblasts. Methods: A cell line of primary human fibroblasts (CCL-210) was cultured on 6-well plates and exposed to varying concentrations of PM2.5 (.01 to 50 ug/cm2) for 24-72 hours. PM2.5 derived from Washington DC and the National Institute of Standards and Technology, or obtained from the rooftop of Peking University School of Public Health in Beijing, China, were used to treat cells. After exposure, cells were lysed, and RNA and DNA were collected and analyzed for gene expression and DNA methylation. Results: PM2.5 exposure was found to decrease the expression of Thy-1 and PTGER2, two genes epigenetically downregulated in IPF, in a dose dependent manner. PM2.5 upregulated expression of BMP2, a secreted ligand of the TGF-Beta protein superfamily, consistent with its profibrotic actions. The effects of PM2.5 were observed independent of the presence of TGF-Beta and were seen with both sources of PM2.5. PM2.5 by itself did not affect expression of a-SMA, a marker of myofibroblast differentiation. Conclusions: These findings demonstrate that PM2.5 alters the expression of key genes, including Thy-1, PTGER2, and BMP2 in a manner that is consistent with the changes seen during IPF. These changes in gene expression could contribute to a profibrotic phenotype, and account for the possibility of PM2.5 contributing to either the development or progression of IPF.
Author Block: N. Craig, P. Tripathi, A. Scruggs, S. K. Huang; Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States.
Rationale: Idiopathic pulmonary fibrosis (IPF) is traditionally considered a respiratory disease of unknown cause, but many investigators have suspected certain environmental exposures, such as wood particulates and metal dust, to be important risk factors. Recent studies have shown that exposure to ambient air pollution, including particulate matter (PM2.5), has been associated with more rapid progression of IPF. Despite this epidemiological evidence, the role that air pollution and PM2.5 have in the pathogenesis of IPF remains understudied. As fibroblasts are the major effector cell of fibrosis, we sought to examine the direct effect of PM2.5 on the functions and actions of human lung fibroblasts. Methods: A cell line of primary human fibroblasts (CCL-210) was cultured on 6-well plates and exposed to varying concentrations of PM2.5 (.01 to 50 ug/cm2) for 24-72 hours. PM2.5 derived from Washington DC and the National Institute of Standards and Technology, or obtained from the rooftop of Peking University School of Public Health in Beijing, China, were used to treat cells. After exposure, cells were lysed, and RNA and DNA were collected and analyzed for gene expression and DNA methylation. Results: PM2.5 exposure was found to decrease the expression of Thy-1 and PTGER2, two genes epigenetically downregulated in IPF, in a dose dependent manner. PM2.5 upregulated expression of BMP2, a secreted ligand of the TGF-Beta protein superfamily, consistent with its profibrotic actions. The effects of PM2.5 were observed independent of the presence of TGF-Beta and were seen with both sources of PM2.5. PM2.5 by itself did not affect expression of a-SMA, a marker of myofibroblast differentiation. Conclusions: These findings demonstrate that PM2.5 alters the expression of key genes, including Thy-1, PTGER2, and BMP2 in a manner that is consistent with the changes seen during IPF. These changes in gene expression could contribute to a profibrotic phenotype, and account for the possibility of PM2.5 contributing to either the development or progression of IPF.
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