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

✍ Scribed by Kuwano, Kazuyoshi; Hagimoto, Naoki; Tanaka, Takuo; Kawasaki, Masayuki; Kunitake, Ritsuko; Miyazaki, Hiroyuki; Kaneko, Yumi; Matsuba, Tokuji; Maeyama, Takashige; Hara, Nobuyuki

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 411 KB
• Volume: 190
• Category: Article
• ISSN: 0022-3417
• DOI: 10.1002/(sici)1096-9896(200002)190:2<221::aid-path495>3.0.co;2-j

✦ Synopsis

Up-regulation of Fas and Fas ligand and excessive apoptosis of bronchiolar and alveolar epithelial cells were identi®ed in bleomycin-induced pulmonary ®brosis 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 in¯ammatory 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.