Regulation of connective tissue growth factor expression by prostaglandin E(2)

• Published in: The American journal of physiology Vol. 277; no. 6; p. L1165
• Main Authors: Ricupero, D A, Rishikof, D C, Kuang, P P, Poliks, C F, Goldstein, R H
• Format: Journal Article
• Language: English
• Published: United States 01.12.1999
• Subjects: Blotting, Western; Cells, Cultured; Colforsin - pharmacology; Collagen - genetics; Connective Tissue Growth Factor; Cyclic AMP-Dependent Protein Kinases - metabolism; Cycloheximide - pharmacology; Dinoprostone - pharmacology; Fibroblasts - cytology; Fibroblasts - enzymology; Gene Expression Regulation - drug effects; Growth Substances - analysis; Growth Substances - genetics; Humans; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Lung - cytology; Protein Synthesis Inhibitors - pharmacology; RNA, Messenger - analysis; Transcription, Genetic - drug effects; Transfection; Transforming Growth Factor beta - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajplung.1999.277.6.L1165

Transforming growth factor-beta (TGF-beta) stimulates alpha(1)(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-beta stimulates time- and dose-dependent increases in CTGF mRNA. In TGF-beta-stimulated fibroblasts, maximal levels of CTGF mRNA (3.7-fold above baseline) occur at 6 h. The TGF-beta-stimulated increase in CTGF mRNA was not blocked by cycloheximide. Nuclear run-on analysis indicates that TGF-beta increases the CTGF transcription rate. The TGF-beta-stimulated increases in CTGF transcription and steady-state levels of CTGF mRNA are attenuated in prostaglandin E(2) (PGE(2))-treated fibroblasts. PGE(2) fails to attenuate luciferase activity induced by TGF-beta in fibroblasts transfected with the TGF-beta-responsive luciferase reporter construct p3TP-LUX. In amino acid-deprived fibroblasts, PGE(2) and insulin regulate alpha(1)(I) collagen mRNA levels without affecting CTGF mRNA levels. The data suggest that the regulation of alpha(1)(I) collagen mRNA levels by TGF-beta and PGE(2) may function through both CTGF-dependent and CTGF-independent mechanisms.