Expression of apoptosis-regulatory genes in epithelial cells in pulmonary fibrosis in mice.
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.
Kuwano
K
K
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan.
Hagimoto
N
N
Tanaka
T
T
Kawasaki
M
M
Kunitake
R
R
Miyazaki
H
H
Kaneko
Y
Y
Matsuba
T
T
Maeyama
T
T
Hara
N
N
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001980:Bronchi / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D051379:Mice; D008813:Mice, Inbred ICR; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53