Hepatoma-derived growth factor is involved in lung remodeling by stimulating epithelial growth

Am J Respir Cell Mol Biol. 2004 Apr;30(4):459-69. doi: 10.1165/rcmb.2003-0013OC. Epub 2003 Sep 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bleomycin / adverse effects
  • Bronchi / cytology
  • Bronchi / pathology
  • Cell Division
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • DNA / biosynthesis
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Lung / cytology*
  • Lung / drug effects
  • Lung / physiopathology*
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Protein Transport / physiology
  • Pulmonary Fibrosis / pathology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Up-Regulation


  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Proteins
  • hepatoma-derived growth factor
  • Bleomycin
  • DNA