Regulation of connective tissue growth factor expression by prostaglandin E2.

Transforming growth factor-β (TGF-β) stimulates α1(I) collagen mRNA synthesis in human lung fibroblasts through a mechanism that is partially sensitive to cycloheximide and that may involve synthesis of connective tissue growth factor (CTGF). Northern blot analyses indicate that TGF-β stimulates time- and dose-dependent increases in CTGF mRNA. In TGF-β-stimulated fibroblasts, maximal levels of CTGF mRNA (3.7-fold above baseline) occur at 6 h. The TGF-β-stimulated increase in CTGF mRNA was not blocked by cycloheximide. Nuclear run-on analysis indicates that TGF-β increases the CTGF transcription rate. The TGF-β-stimulated increases in CTGF transcription and steady-state levels of CTGF mRNA are attenuated in prostaglandin E2(PGE2)-treated fibroblasts. PGE2 fails to attenuate luciferase activity induced by TGF-β in fibroblasts transfected with the TGF-β-responsive luciferase reporter construct p3TP-LUX. In amino acid-deprived fibroblasts, PGE2and insulin regulate α1(I) collagen mRNA levels without affecting CTGF mRNA levels. The data suggest that the regulation of α1(I) collagen mRNA levels by TGF-β and PGE2 may function through both CTGF-dependent and CTGF-independent mechanisms.