Liver fibrogenesis due to cholestasis is associated with increased Smad7 expression and Smad3 signaling

Journal of Cellular and Molecular Medicine

Volumn 10, Issue 4, 2006, Pages 922-932

  Seyhan, H ^a   Hamzavi, J ^b   Wiercinska, Eliza ^b   Gressner, A M ^c   Mertens, P R ^c   Kopp, J ^a   Horch, R E ^a   Breitkopf, Katja ^b   Dooley, S ^b  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c UNIVERSITY HOSPITAL RWTH AACHEN   (Germany)

Author keywords

Hepatic stellate cells; Hepatocytes; Liver fibrogenesis; Signal transduction; Smad; TGF

Indexed keywords

MADH3 PROTEIN, RAT; MADH4 PROTEIN, RAT; SMAD3 PROTEIN; SMAD4 PROTEIN; SMAD7 PROTEIN; SMAD7 PROTEIN, RAT; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL; ARTICLE; BILE DUCT; BIOSYNTHESIS; CHOLESTASIS; ENZYMOLOGY; IMMUNOHISTOCHEMISTRY; LIGATION; LIVER; LIVER CIRRHOSIS; MALE; METABOLISM; PATHOLOGY; PHYSIOLOGY; RAT; SIGNAL TRANSDUCTION; SPRAGUE DAWLEY RAT;

ANIMALS; BILE DUCTS; CHOLESTASIS; IMMUNOHISTOCHEMISTRY; LIGATION; LIVER; LIVER CIRRHOSIS; MALE; RATS; RATS, SPRAGUE-DAWLEY; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; SMAD4 PROTEIN; SMAD7 PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

EID: 34547605248     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1582-4934.2006.tb00535.x     Document Type: Article

References (34)

1. Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 2001; 21: 311-35.
2. Friedman SL. Liver fibrosis - from bench to bedside. J Hepatol. 2003; 38: S38-53.
3. Kopp J, Seyhan H, Muller B, Lanczak J, Pausch E, Gressner AM, Dooley S, Horch RE. N-acetyl-L-cysteine abrogates fibrogenic properties of fibroblasts isolated from Dupuytren's disease by blunting TGF-beta signalling. J Cell Mol Med. 2006; 10: 157-65.
4. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis. Front Biosci. 2002; 7: d793-807.
5. ten Dijke P, Hill CS. New insights into TGF -beta-Smad signalling. Trends Biochem Sci. 2004; 29: 265-73.
6. Topper JN, Cai J, Qiu Y, Anderson KR, Xu YY, Deeds JD, Feeley R, Gimeno CJ, Woolf EA, Tayber O, Mays GG, Sampson BA, Schoen FJ, Gimbrone MA, Jr, Falb D. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci USA. 1997; 94: 9314-9.
7. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata N, Heldin NE, Heldin CH, Tendijke P. Identification of Smad7, a TGF beta-inducible antagonist of TGF -beta signalling. Nature 1997; 389: 631-5.
8. Zhu HJ, Iaria J, Sizeland AM. Smad7 differentially regulates transforming growth factor beta-mediated signaling pathways. J Biol Chem. 1999; 274: 32258-64.
9. Afrakhte M, Moren A, Jossan S, Itoh S, Sampath K, Westermark B, Heldin CH, Heldin NE, ten Dijke P. Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members. Biochem Biophys Res Commun. 1998; 249: 505-11.
10. Bitzer M, von Gersdorff G, Liang D, Dominguez-Rosales A, Beg AA, Rojkind M, Bottinger EP. A mechanism of suppression of TGF-beta/SMAD signaling by NF-kappa B/RelA. Genes Dev. 2000; 14: 187-97.
11. Stopa M, Anhuf D, Terstegen L, Gatsios P, Gressner AM, Dooley S. Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF-beta)-induced activation of Smad7. THE TGF-beta response element of the promoter requires functional Smad binding element and E- box sequences for transcriptional regulation. J Biol Chem. 2000; 275: 29308-17.
12. Ulloa L, Doody J, Massague J. Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway. Nature 1999; 397: 710-3.
13. Dooley S, Delvoux B, Lahme B, Mangasser-Stephan K, Gressner AM. Modulation of transforming growth factor beta response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts. Hepatology 2000; 31: 1094-106.
14. Dooley S, Delvoux B, Streckert M, Bonzel L, Stopa M, ten Dijke P, Gressner AM. Transforming growth factor beta signal transduction in hepatic stellate cells via Smad2/3 phosphorylation, a pathway that is abrogated during in vitro progression to myofibroblasts. TGFbeta signal transduction during transdifferentiation of hepatic stellate cells. FEBS Lett. 2001; 502: 4-10.
15. Dooley S, Streckert M, Delvoux B, Gressner AM. Expression of Smads during in vitro transdifferentiation of hepatic stellate cells to myofibroblasts. Biochem Biophys Res Commun. 2001; 283: 554-62.
16. Gressner AM, Weiskirchen R. Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med. 2006; 10: 76-99.
17. Breitkopf K, Lahme B, Tag CG, Gressner AM. Expression and matrix deposition of latent transforming growth factor beta binding proteins in normal and fibrotic rat liver and transdifferentiating hepatic stellate cells in culture. Hepatology 2001; 33: 387-96.
18. Berg F, Delvoux B, Gao C, Westhoff JH, Breitkopf K, Gressner AM. Divergence of TGF-β signaling in activated hepatic stellate cells downstream from Smad2 phosphorylation. Signal Transduction 2002; 1-3: 1-18.
19. Inagaki Y, Mamura M, Kanamaru Y, Greenwel P, Nemoto T, Takehara K, Ten Dijke P, Nakao A. Constitutive phosphorylation and nuclear localization of Smad3 are correlated with increased collagen gene transcription in activated hepatic stellate cells. J Cell Physiol. 2001; 187: 117-23.
20. Dooley S, Hamzavi J, Breitkopf K, Wiercinska E, Said HM, Lorenzen J, Ten Dijke P, Gressner AM. Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats. Gastroenterology 2003; 125: 178-91.
21. Horch RE. Future perspectives in tissue engineering. J Cell Mol Med. 2006; 10: 4-6.
22. Kountouras J, Billing BH, Scheuer PJ. Prolonged bile duct obstruction: A new experimental model for cirrhosis in the rat. Br J Exp Path. 1984; 65: 305-11.
23. Jamall IS, Finelli VN, Que Hee SS A simple method to determine nanogram levels of 4hydroxyproline in biological tissues. Anal Biochem. 1981; 112: 70-5.
24. Tokunaga K, Nakamura Y, Sakata K, Fujimori K, Ohkubo M, Sawada K, Sakiyama S. Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Cancer Res. 1987; 47: 5616-9.
25. George J, Roulot D, Koteliansky VE, Bissell DM. In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: A potential new therapy for hepatic fibrosis. Proc Nat Acad Sci USA. 1999; 96: 12719-24.
26. Qi Z, Atsuchi N, Ooshima A, Takeshita A, Ueno H. Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat. Proc Nat Acad Sci USA. 1999; 96: 2345-9.
27. Yata Y, Gotwals P, Koteliansky V, Rockey DC. Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-beta soluble receptor: implications for antifibrotic therapy. Hepatology 2002; 35: 1022-30.
28. Okuno M, Akita K, Moriwaki H, Kawada N, Ikeda K, Kaneda K, Suzuki Y, Kojima S. Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-beta. Gastroenterology 2001; 120: 1784-800.
29. Tahashi Y, Matsuzaki K, Date M, Yoshida K, Furukawa F, Sugano Y, Matsushita M, Himeno Y, Inagaki Y, Inoue K. Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury. Hepatology 2002; 35: 49-61.
30. Flanders KC. Smad3 as a mediator of the fibrotic response. Int J Exp Pathol. 2004; 85: 47-64.
31. Inagaki Y, Nemoto T, Nakao A, Dijke P, Kobayashi K, Takehara K, Greenwel P. Interaction between GC box binding factors and Smad proteins modulates cell lineage-specific alpha 2(I) collagen gene transcription. J Biol Chem. 2001; 276: 16573-9.
32. Liu C, Gaca MD, Swenson ES, Vellucci VF, Reiss M, Wells RG. Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-betaindependent. J Biol Chem. 2003; 278: 11721-8.
33. Furukawa F, Matsuzaki K, Mori S, Tahashi Y, Yoshida K, Sugano Y, Yamagata H, Matsushita M, Seki T, Inagaki Y, Nishizawa M, Fujisawa J, Inoue K. p38 MAPK mediates fibrogenic signal through Smad3 phosphorylation in rat myofibroblasts. Hepatology 2003; 38: 879-89.
34. Takehara T, Tatsumi T, Suzuki T, Rucker EB, 3rd, Hennighausen L, Jinushi M, Miyagi T, Kanazawa Y, Hayashi N. Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses. Gastroenterology 2004; 127: 1189-97.