Lipopolysaccharide up-regulates platelet-derived growth factor (PDGF) α-receptor expression in rat lung myofibroblasts and enhances response to all PDGF isoforms

Abstract

Differential expression of PDGF receptor α and β subunits controls the response of mesenchymal cells to the three PDGF isoforms (AA, AB, and BB). Cultured rat lung myofibroblasts (RLMF) possess abundant PDGF receptor-β (PDGF-Rβ) and little PDGF receptor-α (PDGF-Rα). Here we show that LPS up-regulates expression of PDGF-Rα and increases the sensitivity of RLMF to all three PDGF isoforms. Treatment of RLMF for 4 to 48 h with LPS enhanced PDGF-Rα surface expression and mRNA 5- to 10-fold but caused no change in expression of PDGF-Rβ. Both RNA and protein synthesis were necessary for up-regulation of PDGF-Rα, and the increase in PDGF-Rα mRNA was most likely regulated at the transcriptional level. PDGF-Rα up-regulation was not mediated by the IL-1R system and was independent of LPS-binding proteins in serum. Highly confluent cultures of RLMF responded more strongly to LPS than did subconfluent cultures. LPS treatment enhanced the mitogenic and chemotactic responses of RLMF to all PDGF isoforms at least threefold. We postulate that signal transduction by PDGF-receptor αβ heterodimers was important in the enhanced responses to PDGF-AB and -BB. We propose that regulation of PDGF-Rα is a critical event in the genesis of pulmonary fibroproliferative diseases.