Regulation of connective tissue growth factor expression by prostaglandin E(2).
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.
Ricupero
D A
DA
Pulmonary Center and Department of Biochemistry, Boston University School of Medicine, Boston 02118-2394, USA. ricupero@bu.edu
Rishikof
D C
DC
Kuang
P P
PP
Poliks
C F
CF
Goldstein
R H
RH
D015153:Blotting, Western; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003094:Collagen / Q000235:genetics; D055513:Connective Tissue Growth Factor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000166:cytology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C526317:CCN2 protein, human; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D005576:Colforsin; D003094:Collagen; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone