This Article Full Text Full Text (PDF) All Versions of this Article: 2003-0013OCv1 30/4/459    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mori, M. Articles by Hayashi, S. Search for Related Content PubMed PubMed Citation Articles by Mori, M. Articles by Hayashi, S.

Hepatoma-Derived Growth Factor Is Involved in Lung Remodeling by Stimulating Epithelial Growth

Department of Molecular Medicine, and Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan

Address correspondence to: Masahide Mori, M.D., Ph.D., Department of Internal Medicine, Osaka Chuo Hospital, Umeda, 3-3-30, Kita-ku, Osaka, 530-0001, Japan. E-mail: m-mori{at}osaka-centralhp.jp

Lung epithelial cells have an integral role in the maintenance of lung homeostasis; however, the regulatory mechanism thereof has not been fully clarified. Recently, hepatoma-derived growth factor (HDGF) was reported to be involved in organ development and remodeling through its mitogenic effect. We investigated the biological role of HDGF in lung remodeling. HDGF was more highly expressed in the lungs of idiopathic pulmonary fibrosis, chiefly in the epithelial cells, than in control nonfibrotic lungs. We also confirmed the expression of HDGF protein and mRNA in the lungs of bleomycin-instilled mice, mainly in the bronchial and alveolar epithelial cells, by immunohistochemical analysis and in situ hybridization. We found that recombinant HDGF promoted DNA synthesis in rat alveolar epithelial cells and A549 cells in vitro. Endogenous HDGF overexpressed by gene transfer was translocated into the nucleus and promoted the proliferation of A549 cells. In vivo intratracheal instillation of recombinant HDGF induced the proliferation of bronchial and alveolar epithelial cells without causing marked interstitial inflammation. These findings suggest that HDGF may be involved in lung remodeling after injury by promoting the proliferation of lung epithelial cells, probably in an autocrine manner.

Abbreviations: alveolar epithelial cell, AEC • bronchoalveolar lavage, BAL • bronchoalveolar lavage fluid, BALF • bronchial epithelial cell, BEC • 5-bromo-2'-deoxyuridine, BrdUrd • 3,3'-diaminobenzidine tetrahydrochloride, DAB • hepatoma-derived growth factor, HDGF • hematoxylin-eosin staining, H-E staining • hepatocyte growth factor, HGF • immunohistochemical, IHC • in situ hybridization, ISH • idiopathic pulmonary fibrosis, IPF • keratinocyte growth factor, KGF • 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT • short interfering RNA, siRNA • surfactant protein C, SP-C • transforming growth factor-ß, TGF-ß