Differential effects of tumor necrosis factor-alpha on the expression of fibronectin and collagen genes in cultured bovine endothelial cells.
The effects of recombinant human tumor necrosis factor-alpha (TNF-alpha) on the expression of fibronectin and types (IV), (III), and (I) procollagen genes in cultured bovine pulmonary artery endothelial cells were examined in this study. Findings indicate that TNF-alpha increases steady-state levels of alpha l (IV) and alpha l (III) procollagen mRNAs while it decreases levels of fibronectin and alpha 2 (1) procollagen mRNA and leaves cytoskeletal actin mRNA levels unchanged. Both dose and exposure time moderated these effects. Treatment with TNF-alpha increased the stability of alpha l (IV) procollagen mRNA. The half-life of this mRNA, previously unreported in the literature, was increased by 118%, while the stability of fibronectin mRNA decreased by 44%. The stability of mRNAs for procollagens alpha l (III) and alpha 2 (I) were unchanged. Except in the case of procollagen alpha l (III), these effects were blocked by cycloheximide. Protein production induced by TNF-alpha was evaluated by immunoprecipitating proteins from the media and cell lysates. Our data indicate that TNF-alpha has a strong pretranslational regulatory role in cultured endothelial cell's expression of extracellular matrix protein genes.
Yao
J
J
Department of Medicine, Medical College of Ohio at Toledo 43699, USA.
Bone
R C
RC
Sawhney
R S
RS
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006207:Half-Life; D011233:Precipitin Tests; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011347:Procollagen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004004:Dichlororibofuranosylbenzimidazole