TGF-β Signaltransduktion in der experimentell induzierten Leberfibrose durch die Gallengangsligatur bei der Ratte

Background/Aims: Profibrogenic TGF-beta signaling in hepatic stellate cells is modulated during transdifferentiation. Strategies to abrogate TGF-beta effects provide promising antifibrotic results, however, in vivo data regarding Smad activation during fibrogenesis are scarce. Methods: Here, liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue. Activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin. Cellular localization of Smad3 proteins was demonstrated by immunohistochemistry. RT-PCR for Smad2, 3, 4 and Smad7 was conducted with total RNA and Northern blot analysis for Smad3 and 7 with mRNA. Whole liver lysates were prepared to detect Smad4 by Western blotting. Results: Smad7 expression was continuously increasing with duration of cholestasis. Smad2 and 4 expression levels were unchanged. Smad3 expression was decreased, while hepatocytes of fibrotic lesions exhibited Smad3. Conclusions: Hepatocytes of damaged liver tissue display increased TGF-beta signaling via Smad3. Further, negative feedback regulation of TGF-beta signaling by increased Smad7 expression in activated hepatic stellate cells occurs, however does not interfere with fibrogenesis.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Seyhan, Harun

Contributors dc:contributor

• Dooley, Steven

• info:eu-repo/classification/ddc/610
• Transforming Growth Factor beta
• Transforming Growth Factor beta 1
• Medizin

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123175%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:61515