1,25-Dihydroxyvitamin D3 represses tropoelastin expression by a posttranscriptional mechanism.
Tropoelastin expression is down-regulated by exposure to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and we present data indicating that this repression is primarily controlled by a posttranscriptional mechanism. Steady-state and functional levels of tropoelastin mRNA were coordinately repressed by 10(-7) M 1,25 (OH)2D3 in fetal bovine chondrocytes, but transcription, as determined by nuclear runoff assay, was not appreciably influenced in fetal bovine chondrocytes or in rat lung fibroblasts. Similarly, exposure to 1,25(OH)2D3 did not influence chloramphenicol acetyl-transferase activity expressed by a human tropoelastin promoter-expression construct in either cell type. Exposure to cycloheximide had little effect on tropoelastin mRNA levels in control cells but partially restored tropoelastin mRNA levels in cells pretreated with 1,25(OH)2D3 and prevented repression when added together with 1,25(OH)2D3. Similarly, simultaneous exposure to actinomycin D and 1,25(OH)2D3 attenuated the down-regulation of tropoelastin. These data indicate that repression of tropoelastin steady-state mRNA levels by 1,25(OH)2D3 is primarily mediated by a posttranscriptional mechanism that requires both transcription and protein synthesis for full effect.
Pierce
R A
RA
Dermatology Division, Jewish Hospital at Washington University Medical Center, St. Louis, Missouri 63110.
Kolodziej
M E
ME
Parks
W C
WC
D000818:Animals; D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D002356:Cartilage / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D002474:Cell-Free System; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D014333:Tropoelastin; D015500:Chloramphenicol O-Acetyltransferase; D002117:Calcitriol