title: P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis.
abstract: The tumor suppressor p53 protein is a transcription factor that plays a central role in the cellular response to DNA damage, and it can cause either G1 arrest or apoptosis. Recently, it was shown to induce the tumor suppressor p21Waf1/Cip1/Sdi1 (p21), which inhibits cyclin-CDK complex kinase activity. Although the etiology of idiopathic pulmonary fibrosis (IPF) is still uncertain, it is postulated that IPF begins with an initial inflammatory lesion localized to the alveolus and progresses on to chronic inflammation with alveolitis. We examined whether p53 and p21 are upregulated in association with chronic DNA damage in the bronchial and alveolar epithelial cells in patients with IPF in an attempt to repair the injury. We performed in situ detection of DNA strand breaks or apoptosis (TUNEL) in the tissues as well as immunohistochemistry (IHC) for p53 and p21. Positive signals by TUNEL were detected mainly in the bronchiolar and alveolar epithelial cells in 10 of 14 lung specimens from patients with IPF. On the other hand, no positive signal by TUNEL was detected in normal lung parenchyma or in specimens of pulmonary emphysema. The IHC demonstrated that p53 and p21 were expressed especially in hyperplastic bronchial and alveolar epithelial cells of lung tissues from all patients with IPF, except five specimens for p21. These results are consistent with those obtained by TUNEL. In normal lung parenchyma and specimens of pulmonary emphysema, p53 and p21 were not detected except in scattered alveolar macrophages and in the epithelial cells within localized fibrotic regions. These results suggest that p53 and p21 are upregulated in association with chronic DNA damage, resulting in either G1 arrest or apoptosis so that the DNA damage can be repaired in IPF. We speculate that chronic DNA damage and repair may lead to mutation of the p53 gene and tumorigenesis in IPF.
authors: Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Higashiku, Fukuoka, Japan.
authors: K
authors: K
authors: Kuwano
authors: R
authors: R
authors: Kunitake
authors: M
authors: M
authors: Kawasaki
authors: Y
authors: Y
authors: Nomoto
authors: N
authors: N
authors: Hagimoto
authors: Y
authors: Y
authors: Nakanishi
authors: N
authors: N
authors: Hara
mesh_terms: D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53