RRC ID 1592
Author Inoshima I, Kuwano K, Hamada N, Yoshimi M, Maeyama T, Hagimoto N, Nakanishi Y, Hara N.
Title Induction of CDK inhibitor p21 gene as a new therapeutic strategy against pulmonary fibrosis.
Journal Am J Physiol Lung Cell Mol Physiol
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.
Volume 286(4)
Pages L727-33
Published 2004-4-1
DOI 10.1152/ajplung.00209.2003
PII 286/4/L727
PMID 15003936
MeSH Adenoviridae / genetics Animals Cyclin-Dependent Kinase Inhibitor p21 Cyclins / genetics* Epithelial Cells / pathology Epithelial Cells / physiology Gene Expression Regulation Genetic Therapy* Genetic Vectors Hydroxyproline / metabolism In Situ Nick-End Labeling Male Mice Mice, Inbred C57BL Pulmonary Fibrosis / metabolism Pulmonary Fibrosis / pathology Pulmonary Fibrosis / therapy*
IF 4.418
Times Cited 26
DNA material AxCALacZ (RDB01745)