Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis. Academic Article uri icon

Overview

MeSH

  • Blotting, Northern
  • Humans
  • Pulmonary Alveoli
  • RNA, Messenger
  • Transcription, Genetic

MeSH Major

  • Gene Expression
  • Macrophages
  • Platelet-Derived Growth Factor
  • Pulmonary Fibrosis

abstract

  • Idiopathic pulmonary fibrosis (IPF) is characterized by accumulation of alveolar macrophages spontaneously releasing exaggerated amounts of the potent mesenchymal cell growth factor platelet-derived growth factor (PDGF). To evaluate the relative contribution of the two PDGF genes to this process, PDGF-A and -B gene transcription rates and mRNA levels were examined in normal and IPF alveolar macrophages. While normal alveolar macrophages constitutively transcribe both PDGF-A and PDGF-B genes, LPS stimulation increases the transcription of both genes more than threefold. Importantly, IPF alveolar macrophages spontaneously transcribe both genes at a rate similar to that observed for normal macrophages after in vitro stimulation. Consistent with the transcription data, normal macrophages contain mRNA for both PDGF-A and -B, but PDGF-B mRNA is 10-fold more abundant. Strikingly, in IPF, both PDGF-A and -B mRNA levels were markedly increased, with persistence of the 10-fold dominance of PDGF-B mRNA. Thus, the exaggerated release of PDGF by IPF alveolar macrophages is likely modulated by upregulated PDGF gene transcription rates and concomitantly increased mRNA levels and the persistent 10-fold excess of B greater than A PDGF mRNA suggests that the PDGF released by alveolar macrophages is likely mostly of the potent B-chain homodimeric form.

publication date

  • June 1990

has subject area

  • Blotting, Northern
  • Gene Expression
  • Humans
  • Macrophages
  • Platelet-Derived Growth Factor
  • Pulmonary Alveoli
  • Pulmonary Fibrosis
  • RNA, Messenger
  • Transcription, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC296674

Digital Object Identifier (DOI)

  • 10.1172/JCI114669

PubMed ID

  • 2347924

Additional Document Info

start page

  • 2023

end page

  • 2027

volume

  • 85

number

  • 6