Published ahead of print on September 11, 2003, doi:10.1165/rcmb.2003-0013OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 4, April 2004, 459-469 A more recent version of this article appeared on April 1, 2004
Submitted on January 24, 2003 Hepatoma-derived growth factor is involved in lung remodeling by stimulating epithelial growthMasahide Mori1*,1 Department of Molecular Medicine, Osaka University Graduate School of Medicine(C4), Suita, Osaka, Japan; Department of Internal Medicine, Osaka Chuo Hospital, Osaka, Osaka, Japan, 2 Department of Molecular Medicine, Osaka University Graduate School of Medicine(C4), Suita, Osaka, Japan, 3 Department of Molecular Medicine, Osaka University Graduate School of Medicine(C4), Suita, Osaka, Japan; Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan, 4 Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, 5 Department of Molecular Medicine, Osaka University Graduate School of Medicine(C4), Suita, Osaka, Japan; Department of Internal Medicine, National Kinki-chuo Hospital for Chest Diseases, Sakai, Osaka, Japan * To whom correspondence should be addressed. E-mail: m-mori{at}osaka-chuohp.skz.or.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 non-fibrotic 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 over-expressed 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.
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