Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice.

Abstract

Osteopontin is a multifunctional matricellular protein abundantly expressed during inflammation and repair. Osteopontin deficiency is associated with abnormal wound repair characterized by aberrant collagen fibrillogenesis in the heart and skin. Recent gene microarray studies found that osteopontin is abundantly expressed in both human and mouse lung fibrosis. Macrophages and T cells are known to be major sources of osteopontin. During lung fibrosis, however, osteopontin expression continues to increase when inflammation has receded, suggesting alternative sources of ostepontin during this response. In this study, we demonstrate immunoreactivity for osteopontin in lung epithelial and inflammatory cells in human usual interstitial pneumonitis and murine bleomycin-induced lung fibrosis. After treatment with bleomycin, osteopontin-null mice develop lung fibrosis characterized by dilated distal air spaces and reduced type I collagen expression compared with wild-type controls. There is also a significant decrease in levels of active transforming growth factor-beta(1) and matrix metalloproteinase-2 in osteopontin null mice. Type III collagen expression and total collagenase activity are similar in both groups. These results demonstrate that osteopontin expression is associated with important fibrogenic signals in the lung and that the epithelium may be an important source of osteopontin during lung fibrosis.

• Authors: Jeffrey S Berman, David Serlin, Xinfang Li, Geoffrey Whitley, John Hayes, David C Rishikof, Dennis A Ricupero, Lucy Liaw, Margaret Goetschkes, Anthony W O'Regan
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 286 Issue 6 Pg. L1311-8 (Jun 2004) ISSN: 1040-0605 [Print] United States
• PMID: 14977630 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibiotics, Antineoplastic
• Collagen Type I
• SPP1 protein, human
• Sialoglycoproteins
• Spp1 protein, mouse
• TGFB1 protein, human
• Tgfb1 protein, mouse
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Osteopontin
• Bleomycin
• Matrix Metalloproteinase 2

Topics

• Animals
• Antibiotics, Antineoplastic
• Bleomycin
• Collagen Type I (genetics)
• Female
• Gene Expression
• Male
• Matrix Metalloproteinase 2 (genetics)
• Mice
• Mice, Mutant Strains
• Osteopontin
• Pneumonia (chemically induced, pathology, physiopathology)
• Pulmonary Fibrosis (chemically induced, pathology, physiopathology)
• Sialoglycoproteins (genetics)
• Signal Transduction (physiology)
• Transforming Growth Factor beta (genetics)
• Transforming Growth Factor beta1