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The role of the receptor for advanced glycation end-products in a murine model of silicosis

Ramsgaard, L and Englert, JM and Tobolewski, J and Tomai, L and Fattman, CL and Leme, AS and Kaynar, AM and Shapiro, SD and Enghild, JJ and Oury, TD (2010) The role of the receptor for advanced glycation end-products in a murine model of silicosis. PLoS ONE, 5 (3).

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Background: The role of the receptor for advanced glycation end-products (RAGE) has been shown to differ in two different mouse models of asbestos and bleomycin induced pulmonary fibrosis. RAGE knockout (KO) mice get worse fibrosis when challenged with asbestos, whereas in the bleomycin model they are largely protected against fibrosis. In the current study the role of RAGE in a mouse model of silica induced pulmonary fibrosis was investigated. Methodology/Principal Findings: Wild type (WT) and RAGE KO mice received a single intratracheal (i.t.) instillation of silica in saline or saline alone as vehicle control. Fourteen days after treatment mice were subjected to a lung mechanistic study and the lungs were lavaged and inflammatory cells, protein and TGF-β levels in lavage fluid determined. Lungs were subsequently either fixed for histology or excised for biochemical assessment of fibrosis and determination of RAGE proteinand mRNA levels. There was no difference in the inflammatory response or degree of fibrosis (hydroxyproline levels) in the lungs between WT and RAGE KO mice after silica injury. However, histologically the fibrotic lesions in the RAGE KO mice had a more diffuse alveolar septal fibrosis compared to the nodular fibrosis in WT mice. Furthermore, RAGE KO mice had a significantly higher histologic score, a measure of affected areas of the lung, compared to WT silica treated mice. A lung mechanistic study revealed a significant decrease in lung function after silica compared to control, but no difference between WT and RAGE KO. While a dose response study showed similar degrees of fibrosis after silica treatment in the two strains, the RAGE KO mice had some differences in the inflammatory response compared to WT mice. Conclusions/Significance: Aside from the difference in the fibrotic pattern, these studies showed no indicators of RAGE having an effect on the severity of pulmonary fibrosis following silica injury. © 2010 Ramsgaard et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Ramsgaard, L
Englert, JM
Tobolewski, J
Tomai, L
Fattman, CLcfattman@pitt.eduCFATTMAN
Leme, ASasl15@pitt.eduASL15
Kaynar, AMkaynar@pitt.eduAMK960000-0001-8847-0450
Shapiro, SDsds33@pitt.eduSDS33
Enghild, JJ
Oury, TDtdoury@pitt.eduTDOURY
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0009604
Schools and Programs: School of Public Health > Environmental and Occupational Health
School of Medicine > Critical Care Medicine
Refereed: Yes
MeSH Headings: Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Gene Expression Regulation; Glycosylation End Products, Advanced--metabolism; Hydroxyproline--metabolism; Inflammation; Lung--pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Fibrosis--genetics; Receptors, Immunologic--genetics; Receptors, Immunologic--physiology; Silicosis--metabolism; Transforming Growth Factor beta--metabolism
Other ID: NLM PMC2841632
PubMed Central ID: PMC2841632
PubMed ID: 20333255
Date Deposited: 03 Aug 2012 18:57
Last Modified: 13 Feb 2020 17:55


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