Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis

Josepha Lasky, Luis A. Ortiz, Boihoang Tonthat, Gary W. Hoyle, Miriam Corti, Grace Athas, Giuseppe Lungarella, Arnold Brody, Mitchell Friedman

Research output: Contribution to journalArticlepeer-review

233 Scopus citations

Abstract

Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF- β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin- resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGFβ1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

Original languageEnglish (US)
Pages (from-to)L365-L371
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number2 19-2
DOIs
StatePublished - Aug 1998

Keywords

  • Collagen
  • Mice
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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