p21(Waf1/Cip1/Sdi1) and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis

Kazuyoshi Kuwano, Ritsuko Kunitake, Masayuki Kawasaki, Yoshitugu Nomoto, Naoki Hagimoto, Yoichi Nakanishi, Nobuyuki Hara

研究成果: ジャーナルへの寄稿記事

246 引用 (Scopus)

抄録

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 p21(Waf1/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.

元の言語英語
ページ(範囲)477-483
ページ数7
ジャーナルAmerican Journal of Respiratory and Critical Care Medicine
154
発行部数2
DOI
出版物ステータス出版済み - 1 1 1996

Fingerprint

Idiopathic Pulmonary Fibrosis
DNA Breaks
DNA Damage
In Situ Nick-End Labeling
Alveolar Epithelial Cells
Lung
Pulmonary Emphysema
Apoptosis
Immunohistochemistry
Tumor Suppressor Protein p53
Cyclins
p53 Genes
Alveolar Macrophages
DNA Repair
Carcinogenesis
Transcription Factors
Phosphotransferases
Epithelial Cells
Inflammation
Mutation

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

これを引用

p21(Waf1/Cip1/Sdi1) and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis. / Kuwano, Kazuyoshi; Kunitake, Ritsuko; Kawasaki, Masayuki; Nomoto, Yoshitugu; Hagimoto, Naoki; Nakanishi, Yoichi; Hara, Nobuyuki.

:: American Journal of Respiratory and Critical Care Medicine, 巻 154, 番号 2, 01.01.1996, p. 477-483.

研究成果: ジャーナルへの寄稿記事

Kuwano, Kazuyoshi ; Kunitake, Ritsuko ; Kawasaki, Masayuki ; Nomoto, Yoshitugu ; Hagimoto, Naoki ; Nakanishi, Yoichi ; Hara, Nobuyuki. / p21(Waf1/Cip1/Sdi1) and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis. :: American Journal of Respiratory and Critical Care Medicine. 1996 ; 巻 154, 番号 2. pp. 477-483.
@article{1105608e38d74e4f85ccc53115cbd508,
title = "p21(Waf1/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 p21(Waf1/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.",
author = "Kazuyoshi Kuwano and Ritsuko Kunitake and Masayuki Kawasaki and Yoshitugu Nomoto and Naoki Hagimoto and Yoichi Nakanishi and Nobuyuki Hara",
year = "1996",
month = "1",
day = "1",
doi = "10.1164/ajrccm.154.2.8756825",
language = "English",
volume = "154",
pages = "477--483",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "2",

}

TY - JOUR

T1 - p21(Waf1/Cip1/Sdi1) and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis

AU - Kuwano, Kazuyoshi

AU - Kunitake, Ritsuko

AU - Kawasaki, Masayuki

AU - Nomoto, Yoshitugu

AU - Hagimoto, Naoki

AU - Nakanishi, Yoichi

AU - Hara, Nobuyuki

PY - 1996/1/1

Y1 - 1996/1/1

N2 - 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 p21(Waf1/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.

AB - 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 p21(Waf1/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.

UR - http://www.scopus.com/inward/record.url?scp=0030215822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030215822&partnerID=8YFLogxK

U2 - 10.1164/ajrccm.154.2.8756825

DO - 10.1164/ajrccm.154.2.8756825

M3 - Article

C2 - 8756825

AN - SCOPUS:0030215822

VL - 154

SP - 477

EP - 483

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 2

ER -