Kuwano K, Hagimoto N, Tanaka T, Kawasaki M, Kunitake R, Miyazaki H, Kaneko Y, Matsuba T, Maeyama T, Hara N
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan.
J Pathol. 2000 Feb;190(2):221-9. doi: 10.1002/(SICI)1096-9896(200002)190:2<221::AID-PATH495>3.0.CO;2-J.
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.
在博来霉素诱导的小鼠肺纤维化中，可发现Fas和Fas配体上调以及细支气管和肺泡上皮细胞过度凋亡。本研究假设，除Fas - Fas配体之外的凋亡调节基因，如p53、p21（Waf1/Cip1）、bcl - 2、bcl - x和bax，也可能参与该模型中的上皮细胞凋亡。通过逆转录聚合酶链反应（RT - PCR）、原位RT - PCR或免疫组织化学评估这些基因的表达。在气管内滴注博来霉素后1小时至7天，肺泡上皮细胞中p53和p21 mRNA的表达同时上调。bcl - 2 mRNA的表达在1小时至14天微弱上调，而bcl - 2蛋白的表达水平未改变。bcl - x(L)和bax mRNA的表达在1小时至7天强烈上调。bcl - x蛋白在淋巴细胞和巨噬细胞中表达上调，而bax蛋白在上皮细胞和炎症细胞中均上调。结论是，除Fas - Fas配体途径上调外，该模型中的上皮细胞凋亡也可能由p53和bax上调以及凋亡诱导基因与抑制基因之间的失衡所诱导。
