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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.241 5-Year IF: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvPathToxOncol.v23.i4.20
14 pages

Effect of Platelet-Derived Growth Factor on the Development and Persistence of Asbestos-Induced Fibroproliferative Lung Disease

Jian Li
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine; and The Interdisciplinary Graduate Program in Molecular and Cellular Biology, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Halet G. Poovey
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Juan Felipe Rodriguez
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Arnold Brody
Department of Pathology and Laboratory Medicine, Tulane University Medical Center 1430 Tulane Avenue New Orleans, LA 70112-2699, USA
Gary W. Hoyle
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana,USA

ABSTRACT

Platelet-derived growth factor (PDGF) isoforms and PDGF receptor-α are upregulated in fibroproliferative lesions in response to asbestos exposure. To examine the functional role of PDGF in asbestos-induced lung disease, we have evaluated the impact of PDGF-B overexpression in the lung on the development of pulmonary fibrosis induced by asbestos inhalation. Transgenic mice expressing PDGF-B from the surfactant protein C promoter and wild-type C57BL/6 mice were exposed to aerosolized chrysotile asbestos fibers via three different exposure regimens: 3 consecutive days to 9 mg/m3, once a week for 5 weeks to 12 mg/m3, or once a week for 8 weeks to 11 mg/m3. The 3-day exposure did not produce fibroproliferative lesions in SPC-PDGFB or wild-type mice, indicating that PDGF expression did not increase susceptibility to a subthreshold dose of asbestos. Transgenic and wild-type mice subjected to the 5-week exposure protocol exhibited similar fibrogenic lesions histologically 48 hours and 8 weeks postexposure, but lungs from transgenic mice had elevated lung hydroxyproline content 8 weeks postexposure relative to wild-type mice. In addition, SPC-PDGFB transgenic mice developed pronounced thickening of arterioles following the 5-week exposure regimen. Mice exposed to asbestos for 8 weeks and examined 10 months later showed pronounced, diffuse fibrotic lesions of terminal bronchioles and alveolar ducts, but no histological differences between transgenic and nontransgenic mice were observed. These results indicated that PDGF-B overexpression can stimulate increased collagen deposition and vascular smooth muscle hyper-plasia following asbestos inhalation and that a limited exposure (8 times) to chrysotile aerosol can produce long-lasting fibrotic lesions. The 8-week exposure regimen provides an animal model that encompasses an important aspect of human asbestosis—i.e., persistence of fibrosis for long periods after cessation of asbestos exposure.


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