ALUNG December 21/6

Ricupero, Dennis A., David C. Rishikof, Ping-Ping Kuang, Christine F. Poliks, and Ronald H. Goldstein. Regulation of connective tissue growth factor expression by prostaglandin E2. Am. J. Physiol. 277 (Lung Cell. Mol. Physiol. 21): L1165–L1171, 1999.—Transforming growth factor-b (TGF-b) stimulates a1(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-b stimulates timeand dosedependent increases in CTGF mRNA. In TGF-b-stimulated fibroblasts, maximal levels of CTGF mRNA (3.7-fold above baseline) occur at 6 h. The TGF-b-stimulated increase in CTGF mRNA was not blocked by cycloheximide. Nuclear run-on analysis indicates that TGF-b increases the CTGF transcription rate. The TGF-b-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-b in fibroblasts transfected with the TGF-b-responsive luciferase reporter construct p3TP-LUX. In amino acid-deprived fibroblasts, PGE2 and insulin regulate a1(I) collagen mRNA levels without affecting CTGF mRNA levels. The data suggest that the regulation of a1(I) collagen mRNA levels by TGF-b and PGE2 may function through both CTGF-dependent and CTGF-independent mechanisms.