Corticosteroids stimulate selectively transforming growth factor (TGF)-beta receptor type III expression in transdifferentiating hepatic stellate cells.
OBJECTIVE
Transforming growth factor (TGF)-beta receptors mediate TGF-beta 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-beta signaling pathway on the transcriptional and translational level.


METHODS
To characterize TGF-beta 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-beta receptor mRNAs are present in HSC and myofibroblasts. Whereas TGF beta receptor type I (T beta RI) shows a comparable mRNA expression during HSC transdifferentiation, T beta RII and T beta RIII mRNA concentration decreases in the course of time. In comparison with activated HSC T beta RIII mRNA is very low expressed in freshly isolated Kupffer cells and hepatocytes. Eight hours after corticosteroid treatment T beta RIII mRNA increased significantly in a time-and dose-dependent manner while the mRNA expression of T beta RI and T beta RII is not altered. The degree of induction of T beta RIII mRNA levels is also dependent upon the nature of the stimulating hormone: dexamethasone, hydrocortisone and aldosterone show different effects.


CONCLUSIONS
The increase of T beta RIII by corticosteroids indicates that these hormones are important regulators of this receptor and thereby they can modulate TGF-beta signaling.
Wickert
Lucia
L
Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany. wickert@unicum.de
Abiaka
Muna
M
Bolkenius
Ursula
U
Gressner
Axel M
AM
D030201:Activin Receptors, Type I / Q000235:genetics; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003199:Computer Systems; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011965:Receptors, Glucocorticoid / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D011509:Proteoglycans; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D000450:Aldosterone; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; D006854:Hydrocortisone