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Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V 2 O 5 )
Author(s) -
Walters Dianne M.,
White Kevin M.,
Patel Ushma,
Davis Martin J.,
VeluciMarlow Roberta M.,
Sunkesula Solomon Raju Bhupanapadu,
Bonner James C.,
Martin Jessica R.,
Gladwell Wes,
Kleeberger Steven R.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-235044
Subject(s) - fibrosis , inbred strain , pentoxide , lung , vanadium , inflammation , pulmonary fibrosis , pathology , gene , chemistry , medicine , immunology , genetics , biology , inorganic chemistry
Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and scarring of alveoli, leading to impaired function. The etiology of idiopathic forms of ILD is not understood, making them particularly difficult to study due to the lack of appropriate animal models. Consequently, few effective therapies have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide (V 2 O 5 ), the most common form of a transition metal found in cigarette smoke, fuel ash, mineral ores, and steel alloys. Pulmonary responses to V 2 O 5 , including dose‐dependent increases in lung permeability, inflammation, collagen content, and dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice. Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while limited responses in C57BL/6J mice resolved. We investigated the genetic basis for differential responses through genetic mapping of V 2 O 5 ‐induced lung collagen content in BXD recombinant inbred (RI) strains and identified significant linkage on chromosome 4 with candidate genes that associate with V 2 O 5 ‐induced collagen content across the RI strains. Results suggest that V 2 O 5 may induce pulmonary fibrosis through mechanisms distinct from those in other models of pulmonary fibrosis. These findings should further advance our understanding of mechanisms involved in ILD and thereby aid in identification of new therapeutic targets.—Walters, D. M., White, K. M., Patel, U., Davis, M. J., Veluci‐Marlow, R. M., Bhupanapadu Sunkesula, S. R., Bonner, J. C., Martin, J. R., Gladwell, W., Kleeberger, S. R. Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V 2 O 5 ). FASEB J. 28, 1098–1112 (2014). www.fasebj.org