Pretranslational regulation of type I collagen, fibronectin, and a 50-kilodalton noncollagenous extracellular protein by dexamethasone in rat fibroblasts.
J Biol Chem
; 261(10): 4677-84, 1986 Apr 05.
Article
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| MEDLINE
| ID: mdl-3957912
ABSTRACT
The effect of dexamethasone on the synthesis of total cellular and extracellular proteins and specifically on the synthesis of type I procollagen chains, fibronectin, and a 50-kDa extracellular noncollagenous polypeptide was examined in cultured rat dermal fibroblasts. A slight but consistent inhibition of total protein synthesis by dexamethasone was dose and time dependent. Treatment of cells with 1 microM dexamethasone for 24 h while abolishing procollagen synthesis nearly completely (less than 95%) had the opposite effect (5-7-fold increase) on the synthesis of an extracellular noncollagenous 50-kDa polypeptide. Dexamethasone did not significantly affect the rates of synthesis of fibronectin. Cell-free translation of mRNA from dexamethasone-treated cells revealed corresponding changes in the steady-state levels of functional mRNAs coding for procollagens, the 50-kDa polypeptide, and fibronectin. Northern blot hybridization using nick-translated cDNA plasmids coding for pro-alpha 1(I), fibronectin, and cytoplasmic beta-actin mRNA corroborated the data obtained from cell-free translation experiments. Run-off transcription assays using nuclei from cells treated with 1 microM dexamethasone for 24 h revealed that glucocorticoid treatment did not significantly affect the rate of transcription of type I collagen genes; similarly, the rate of transcription of fibronectin and cytoplasmic beta-actin genes also remained unchanged under these conditions. An analysis of the kinetics of decay of radiolabeled mRNA coding for pro-alpha 1(I), pro-alpha 2(I), and fibronectin in dexamethasone-treated cells revealed that procollagen mRNAs were turned over at an accelerated rate in glucocorticoid-treated cells. These data suggest that dexamethasone regulates type I collagen gene expression by preferentially decreasing the stability of pro-alpha 1(I) and pro-alpha2(I) mRNAs. Although dexamethasone increased the levels of translatable mRNAs coding for a 50-kDa polypeptide, the molecular mechanism(s) of how hormone exerts this effect remains unknown.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dexametasona
/
Proteínas
/
Procesamiento Proteico-Postraduccional
/
Colágeno
/
Fibronectinas
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
1986
Tipo del documento:
Article