Expression of apoptosis-regulatory genes in epithelial cells in pulmonary fibrosis in mice

被引:12
作者
Kuwano, K [1 ]
Hagimoto, N [1 ]
Tanaka, T [1 ]
Kawasaki, M [1 ]
Kunitake, R [1 ]
Miyazaki, H [1 ]
Kaneko, Y [1 ]
Matsuba, T [1 ]
Maeyama, T [1 ]
Hara, N [1 ]
机构
[1] Kyushu Univ, Fac Med, Chest Dis Res Inst, Higashi Ku, Fukuoka 812, Japan
关键词
Fas; Fas ligand; p53; p21; bcl-2; bcl-x; bax; apoptosis; bleomycin; pulmonary fibrosis;
D O I
10.1002/(SICI)1096-9896(200002)190:2<221::AID-PATH495>3.0.CO;2-J
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 upregulated 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 Pas-Fas ligand pathway, Copyright (C) 2000 John Wiley & Sons, Ltd.
引用
收藏
页码:221 / 229
页数:9
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