Corticosteroids stimulate selectively transforming growth factor (TGF)-β receptor type III expression in transdifferentiating hepatic stellate cells
| Autor: | M. Abiaka, U. Bolkenius, Axel M. Gressner, Lucia Wickert |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Hydrocortisone Transcription Genetic Receptor expression Receptor Transforming Growth Factor-beta Type I Protein Serine-Threonine Kinases Biology Polymerase Chain Reaction Dexamethasone Rats Sprague-Dawley Receptors Glucocorticoid Glucocorticoid receptor Adrenal Cortex Hormones Computer Systems Internal medicine medicine Animals RNA Messenger Receptor Aldosterone Glucocorticoids Cells Cultured R-SMAD Hepatology Receptor Transforming Growth Factor-beta Type II Cell Differentiation TGF beta receptor 2 Lipid Metabolism Rats Cell biology Endocrinology Liver Hepatic stellate cell Proteoglycans Signal transduction Activin Receptors Type I Receptors Transforming Growth Factor beta Signal Transduction Transforming growth factor |
| Zdroj: | Journal of Hepatology. 40:69-76 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2003.09.026 |
| Popis: | Background/Aims : Transforming growth factor (TGF)-β receptors mediate TGF-β signaling in activated hepatic stellate cells (HSC). This leads to pleiotropic cellular effects, e.g. to the production of extracellular matrix which is a hallmark for the development of liver fibrosis. Glucocorticoids and their receptors interact with the TGF-β signaling pathway on the transcriptional and translational level. Methods : To characterize TGF-β receptor expression during HSC transdifferentiation and to study the influence of corticosteroids on receptor transcription in several liver cells, we established a real-time polymerase chain reaction procedure for mRNA quantification with gene-specific standards. Results : All three TGF-β receptor mRNAs are present in HSC and myofibroblasts. Whereas TGFβ receptor type I (TβRI) shows a comparable mRNA expression during HSC transdifferentiation, TβRII and TβRIII mRNA concentration decreases in the course of time. In comparison with activated HSC TβRIII mRNA is very low expressed in freshly isolated Kupffer cells and hepatocytes. Eight hours after corticosteroid treatment TβRIII mRNA increased significantly in a time-and dose-dependent manner while the mRNA expression of TβRI and TβRII is not altered. The degree of induction of TβRIII mRNA levels is also dependent upon the nature of the stimulating hormone: dexamethasone, hydrocortisone and aldosterone show different effects. Conclusions : The increase of TβRIII by corticosteroids indicates that these hormones are important regulators of this receptor and thereby they can modulate TGF-β signaling. |
| Databáze: | OpenAIRE |
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