Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis.
| Publication Type | Academic Article |
| Authors | Nagaoka I, Trapnell B, Crystal R |
| Journal | J Clin Invest |
| Volume | 85 |
| Issue | 6 |
| Pagination | 2023-7 |
| Date Published | 06/01/1990 |
| ISSN | 0021-9738 |
| Keywords | 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. |
| DOI | 10.1172/JCI114669 |
| PubMed ID | 2347924 |
| PubMed Central ID | PMC296674 |