Enhanced insulin-like growth factor molecules in idiopathic pulmonary fibrosis

Christopher Aston, Jaishree Jagirdar, Theodore C. Lee, Tau Hur, Raymond L. Hintz, William N. Rom

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Idiopathic pulmonary fibrosis (IPF) is characterized by activated alveolar macrophages (AM), alveolar epithelial call proliferation and interstitial matrix, and immune complex deposition. Spontaneous release of competence and progression-type growth factors and their associated binding proteins may contribute to the pathologic features of IPF. To study the role of insulin like growth factor (IGF) molecules in IPF we evaluated spontaneous release of IGF-1 and IGFBP-3 in bronchoalveolar lavage cells from control subjects and from patients with IPF. IGF-1 levels were similar compared with those in control subjects. In contrast, IGFBP-3 was significantly increased in IPF. In situ hybridization of open lung biopsies showed IGF-1 to be abundant in IPF lung tissue in alveolar macrophages, interstitial mesenchymal cells, and epithelial cells. Northern, Western ligand blotting, reverse transcription PCR, and radioimmunoassay suggested that immune complexes stimulate expression of IGFBP-3 in mononuclear phagocytes in a time- and dose-dependent manner bearing strong similarities to stimulation by LPS. These data are compatible with the hypothesis that IGFBP-3 increases the bioactivity of IGF- 1 derived from a variety of lung tissues contributing to the fibrosis and remodeling seen in IPF.

Original languageEnglish (US)
Pages (from-to)1597-1603
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number5
StatePublished - May 1995

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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