Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis

Pardo, A and Gibson, K and Cisneros, J and Richards, TJ and Yang, Y and Becerril, C and Yousem, S and Herrera, I and Ruiz, V and Selman, M and Kaminski, N (2005) Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis. PLoS Medicine, 2 (9). 0891 - 0903. ISSN 1549-1277

[img]
Preview
 PDF
Published Version
Available under License : See the attached license file.
Download (412kB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.
Download (1kB)

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung. Methods and Findings: Using oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF lungs and was also significantly elevated in bronchoalveolar lavage from IPF patients. To study the fibrosis-relevant effects of osteopontin we stimulated primary human lung fibroblasts and alveolar epithelial cells (A549) with recombinant osteopontin. Osteopontin induced a significant increase of migration and proliferation in both fibroblasts and epithelial cells. Epithelial growth was inhibited by the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) and antibody to CD44, while fibroproliferation was inhibited by GRGDS and antibody to avb3 integrin. Fibroblast and epithelial cell migration were inhibited by GRGDS, anti-CD44, and anti- αvβ3. In fibroblasts, osteopontin up-regulated tissue inhibitor of metalloprotease-1 and type I collagen, and down-regulated matrix metalloprotease-1 (MMP-1) expression, while in A549 cells it caused up-regulation of MMP-7. In human IPF lungs, osteopontin colocalized with MMP-7 in alveolar epithelial cells, and application of weakest link statistical models to microarray data suggested a significant interaction between osteopontin and MMP-7. Conclusions: Our results provide a potential mechanism by which osteopontin secreted from the alveolar epithelium may exert a profibrotic effect in IPF lungs and highlight osteopontin as a potential target for therapeutic intervention in this incurable disease. © 2005 Pardo et al.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pardo, A
Gibson, Kkfg@pitt.eduKFG
Cisneros, J
Richards, TJ
Yang, Y
Becerril, C
Yousem, Syousem@pitt.eduYOUSEM
Herrera, I
Ruiz, V
Selman, M
Kaminski, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBarnes, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 7 October 2005
Date Type: Publication
Journal or Publication Title: PLoS Medicine
Volume: 2
Number: 9
Page Range: 0891 - 0903
DOI or Unique Handle: 10.1371/journal.pmed.0020251
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
ISSN: 1549-1277
PubMed ID: 16128620
Date Deposited: 11 Jul 2012 17:51
Last Modified: 22 Jun 2021 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/12835

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

Actions (login required)

View Item View Item