Corticosteroids stimulate selectively transforming growth factor (TGF)-β receptor type III expression in transdifferentiating hepatic stellate cells

• Published in: Journal of hepatology 2004, Vol.40 (1), p.69-76
• Main Authors: Wickert, Lucia, Abiaka, Muna, Bolkenius, Ursula, Gressner, Axel M
• Format: Article
• Language: English
• Subjects: Activated hepatic stellate cells; Activin Receptors, Type I - genetics; Adrenal Cortex Hormones - pharmacology; Aldosterone - pharmacology; Animals; Biological and medical sciences; Cell Differentiation; Cells, Cultured; Computer Systems; Corticosteroids; Dexamethasone - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Gene-specific standards; Glucocorticoid receptor; Glucocorticoids - pharmacology; Hydrocortisone - pharmacology; Lipid Metabolism; Liver - cytology; Liver - drug effects; Liver - metabolism; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver Cirrhosis - physiopathology; Male; Medical sciences; Polymerase Chain Reaction - methods; Protein-Serine-Threonine Kinases; Proteoglycans - genetics; Proteoglycans - metabolism; Rats; Rats, Sprague-Dawley; Real-time polymerase chain reaction; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Receptors, Glucocorticoid - physiology; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; RNA, Messenger - metabolism; Signal Transduction - physiology; Transcription, Genetic; Transforming growth factor-β-receptors
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2003.09.026

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.