The role of strain variation in BAX and BCL-2 expression in murine bleomycin-induced pulmonary fibrosis.
This study hypothesized that the expression of apoptosis-regulatory genes, such as BCL-2 and BAX may be affected by genetic variation in bleomycin-induced pulmonary fibrosis in C57BL/6 and NMRI mice. Pulmonary fibrosis induced by single intratracheal dose of bleomycin (3 U kg(-1)). After 2 weeks, lung samples were analyzed for collagen deposition, pathological changes and expression of BCL-2 and BAX. The fibrotic lung changes were similar in both strains. The immunohistochemical assay using a biotin-streptavidin technique showed no significant difference in immunoreactivity for BCL-2 protein between the controls and bleomycin-treated C57BL/6 mice. However, in NMRI mice, the expression of BCL-2 was significantly (p<0.05) upregulated in myofibroblasts and neutrophils. The expression of BAX protein was significantly (p<0.05) upregulated in alveolar epithelial cells of both strains and downregulated in myofibroblasts and lymphocytes of the lung tissues of C57BL/6 mice and also in lymphocytes of NMRI mice at 2 weeks after bleomycin instillation. These results confirm the role of BCL-2 and BAX proteins in the pathogenesis of pulmonary fibrosis and suggest that the expression of apoptotic regulatory genes may be specific in different cell types in various strains.
Safaeian
L
L
Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Hezar Jarib Avenue, Isfahan, Iran.
Jafarian
A
A
Rabbani
M
M
Sadeghi
H M
HM
Torabinia
N
N
Alavi
S A
SA
D000818:Animals; D001761:Bleomycin; D005786:Gene Expression Regulation / Q000187:drug effects; D014644:Genetic Variation; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D013045:Species Specificity; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001761:Bleomycin