BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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.
Authors: Maria Irma Seixas Duarte; Heitor Franco de Andrade; Cleusa Fumica Hirata Takamura; Antonio Sesso; Felipe Francisco Tuon Journal: Parasitol Res Date: 2008-12-05 Impact factor: 2.289