Induction of CDK inhibitor p21 gene as a new therapeutic strategy against pulmonary fibrosis

Ichiro Inoshima, Kazuyoshi Kuwano, Naoki Hamada, Michihiro Yoshimi, Takashige Maeyama, Naoki Hagimoto, Yoichi Nakanishi, Nobuyuki Hara

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Abstract

Alveolar epithelial cells are known to be present at the primary site of lung damage in pulmonary fibrosis. Apoptosis has been implicated as being involved in epithelial cell damage and pulmonary fibrosis. Because the cyclin-dependent kinase inhibitor p21 induces G1 arrest and DNA repair and because it also prevents apoptosis in some cells, we hypothesized that p21 gene transfer may attenuate bleomycin-induced pulmonary fibrosis in mice, the pathogenesis of which likely involves epithelial cell apoptosis. Human p21 protein was expressed in mouse alveolar epithelial cells at 1-7 days in vitro and was detected predominantly in lung epithelial cells at 1-7 days in vivo after adenoviral transfer of the human p21 gene. Inflammatory cell infiltration and fibrosis had already begun at 7 days in this model. Adenoviral transfer of the human p21 gene at 7 days after intratracheal instillation of bleomycin led to a decrease in the number of apoptotic cells, lung inflammation, and fibrosis at 14 days. Therefore, the forced expression of p21 exerted both anti-apoptotic and anti-fibrotic effects, which would facilitate the ultimate goal of treatment for pulmonary fibrosis.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume286
Issue number4 30-4
Publication statusPublished - Apr 1 2004

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Pulmonary Fibrosis
Alveolar Epithelial Cells
Epithelial Cells
Bleomycin
Apoptosis
Genes
Fibrosis
Cyclin-Dependent Kinase Inhibitor p21
Lung
Therapeutics
DNA Repair
Pneumonia
Cell Count

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Induction of CDK inhibitor p21 gene as a new therapeutic strategy against pulmonary fibrosis. / Inoshima, Ichiro; Kuwano, Kazuyoshi; Hamada, Naoki; Yoshimi, Michihiro; Maeyama, Takashige; Hagimoto, Naoki; Nakanishi, Yoichi; Hara, Nobuyuki.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 286, No. 4 30-4, 01.04.2004.

Research output: Contribution to journalArticle

Inoshima, I, Kuwano, K, Hamada, N, Yoshimi, M, Maeyama, T, Hagimoto, N, Nakanishi, Y & Hara, N 2004, 'Induction of CDK inhibitor p21 gene as a new therapeutic strategy against pulmonary fibrosis', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 286, no. 4 30-4.
Inoshima, Ichiro ; Kuwano, Kazuyoshi ; Hamada, Naoki ; Yoshimi, Michihiro ; Maeyama, Takashige ; Hagimoto, Naoki ; Nakanishi, Yoichi ; Hara, Nobuyuki. / Induction of CDK inhibitor p21 gene as a new therapeutic strategy against pulmonary fibrosis. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2004 ; Vol. 286, No. 4 30-4.
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