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Expression of apoptosis‐regulatory genes in epithelial cells in pulmonary fibrosis in mice
Author(s) -
Kuwano Kazuyoshi,
Hagimoto Naoki,
Tanaka Takuo,
Kawasaki Masayuki,
Kunitake Ritsuko,
Miyazaki Hiroyuki,
Kaneko Yumi,
Matsuba Tokuji,
Maeyama Takashige,
Hara Nobuyuki
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(200002)190:2<221::aid-path495>3.0.co;2-j
Subject(s) - apoptosis , bleomycin , fas ligand , microbiology and biotechnology , pulmonary fibrosis , messenger rna , biology , gene expression , bcl 2 associated x protein , gene , cancer research , fibrosis , programmed cell death , pathology , medicine , caspase 3 , genetics , chemotherapy
Up‐regulation of Fas and Fas ligand and excessive apoptosis of bronchiolar and alveolar epithelial cells were identified in bleomycin‐induced pulmonary fibrosis in mice. This study hypothesized that apoptosis‐regulatory genes other than Fas–Fas ligand, such as p53, p21 (Waf1/Cip1), bcl‐2, bcl‐x, and bax, may also participate in epithelial cell apoptosis in this model. The expression of these genes was assessed by reverse transcription polymerase chain reaction (RT‐PCR), RT in situ PCR, or immunohistochemistry. The expression of p53 and p21 mRNA was concurrently up‐regulated in the alveolar epithelial cells at 1 h to 7 days after intratracheal instillation of bleomycin. The expression of bcl‐2 mRNA was weakly up‐regulated at 1 h to 14 days, while the expression level of bcl‐2 protein was not changed. The expression of bcl‐x(L) and bax mRNA was strongly up‐regulated at 1 h to 7 days. The expression of bcl‐x protein was up‐regulated in lymphocytes and macrophages, whereas bax protein was up‐regulated in both epithelial and inflammatory cells. It is concluded that epithelial cell apoptosis in this model may also be induced by the up‐regulation of p53 and bax and by the imbalance between apoptosis‐inducible and ‐inhibitory genes, in addition to the up‐regulation of the Fas–Fas ligand pathway. Copyright © 2000 John Wiley & Sons, Ltd.