Dexamethasone activates expression of the PDGF-α receptor and induces lung fibroblast proliferation

G. Sakuntala Warshamana, Sylvia Martinez, Joseph A. Lasky, Miriam Corti, Arnold R. Brody

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understand the mechanisms through which CSs control cell proliferation, we have carried out experiments to test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiescent cells in 1% serum or in serum- free media proliferate significantly in response to the addition of 10-7 to 10-9 M Dex. Increases as high as fourfold in cell numbers were recorded for the RLFs after 48 h in culture. A polyclonal antibody to the AB isoform of human platelet-derived growth factor (PDGF) blocked the proliferative response. As expected, the fibroblasts produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-α receptors (PDGF-Rα), the receptor type necessary for binding the AA isoform. Accordingly, we determined that Dex upregulated PDGF-Rα mRNA and protein. Therefore, we can postulate that Dex- induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-Rα.

Original languageEnglish (US)
Pages (from-to)L499-L507
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number4 18-4
DOIs
StatePublished - Apr 1998

Keywords

  • Anti-platelet-derived growth factor
  • Platelet-derived growth factor isoforms
  • Platelet-derived growth factor-α receptor

ASJC Scopus subject areas

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

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