Fibrotic gene expression coexists with alveolar proteinosis in early indium lung.
Occupational inhalation of indium compounds can cause the so-called "indium lung disease". Most affected individuals show pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease. In animal experiments, inhalation of indium tin oxide or indium oxide has been shown to cause lung damage. However, the mechanisms by which indium compounds lead to indium lung disease remain unknown. In this study, we constructed a mouse model of indium lung disease and analyzed gene expression in response to indium exposure. Indium oxide (In2O3, 10 mg/kg, primary particle size <100 nm) was administered intratracheally to C57BL/6 mice (male, 8 weeks of age) twice a week for 8 weeks. Four weeks after the final instillation, histopathological analysis exhibited periodic acid-Schiff positive material in the alveoli, characteristic of PAP. Comprehensive gene expression analysis by RNA-Seq, however, revealed expression of fibrosis-related genes, such as surfactant associated protein D, surfactant associated protein A1, mucin 1, and collagen type I and III, was significantly increased, indicating that fibrotic gene expression progresses in early phase of indium lung. These data supported the latest hypothesis that PAP occurs as an acute phase response and is replaced by fibrosis after long-term latency.
a Department of Environmental Medicine , Kochi Medical School, Kochi University , Kochi , Japan.
Shuhei
S
Noguchi
a Department of Environmental Medicine , Kochi Medical School, Kochi University , Kochi , Japan.
Masamitsu
M
Eitoku
a Department of Environmental Medicine , Kochi Medical School, Kochi University , Kochi , Japan.
Hidenori
H
Kiyosawa
a Department of Environmental Medicine , Kochi Medical School, Kochi University , Kochi , Japan.
Narufumi
N
Suganuma
D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects*; D007204:Indium / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects*; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000235:genetics; D010316:Particle Size; D011649:Pulmonary Alveolar Proteinosis / Q000139:chemically induced* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics
D024042:Collagen Type I; D024061:Collagen Type III; D018396:Mucin-1; D037661:Pulmonary Surfactant-Associated Proteins; D007204:Indium; C047711:indium oxide
Fibrosis; RNA-Seq; indium lung disease; indium oxide; intratracheal administration; mouse model; pulmonary alveolar proteinosis