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Does liver fibrosis represent a reversible process?


Authors: Bittnerová Lenka
Authors‘ workplace: Univerzita Karlova v Praze, Lékařská fakulta v Hradci Králové: Ústav lékařské biochemie, přednostka doc. MUDr. Martina Řezáčová, Ph. D.
Published in: Pracov. Lék., 65, 2013, No. 1-2, s. 48-52.
Category: Review Article

Overview

Liver fibrosis if the consequence of most diverse causes or stimuli – it is the consequence chronic liver diseases such as virus hepatitis or autoimmune hepatitis, alcohol abuse, effects of toxins or biliary damage. In occupational pathology we rarely encounter the action of hepatotoxic substances. Necrosis of hepatocytes follows to activation of hepatic stellate cells (HSC) and activation of a whole series of immune cells. HSCs play a principal role in fibrogenesis, produce collagen Type I and other components of extracellular matrix, which are accumulated and stored in liver. HSCs release various profibrogenic cytokines, metalloproteases and inhibitors of matrix-degrading enzymes, which are necessary for the whole process and play a key role there. Experimental studies demonstrated reversibility of the fibrotic process, while a definite possibility to remove superfluous HSCs is to decrease their number by apoptosis. Therefore, induction or influence of HSCs apoptosis is presently a significant strategic-therapeutic and antifibrotic goal. The paper pays attention to etiological aspects, molecular pathogenesis of liver fibrosis and possibility of reversibility.

Keywords:
fibrosis – liver stellate cells – apoptosis – extracellular matrix


Sources

1. Bataller, R., Brenner, D. A. Liver fibrosis. J. Clin. Invest., 2005; 115 (2):209-18. Review. Erratum in: J. Clin. Invest., 2005 Apr;115(4):1100.

2. Bedossa, P., Paradis, V. Liver extracellular matrix in health and disease. J. Pathol., 2003, 200 (4), s. 504–515. Review.

3. Benyon, R. C., Iredale, J. P. Is liver fibrosis reversible? Gut, 2000 Apr, 46 (4), s. 443–446.

4. Brhel, P., Picka, K., Hrubá, D. Úvod do průmyslové toxikologie. LFMU Brno 1998, s. 19–21.

5. Canbay A., Friedman S, Gores G. Apoptosis: The nexus of liver and fibrosis. Hematology, 2004, 39, s. 273–278.

6. Elsharkawy, A. M., Oakley, F., Mann, D. A. The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. Apoptosis, 2005 Oct;10 (5), s. 927–939.

7. Friedman S. L. Mechanisms of hepatic fibrogenesis. Gastroenterology, vol. 134, no. 6, pp. 1655–1669, 2008.

8. Friedman, S. L., Bansal, M. B. Reversal of hepatic fibrosis – fact or fantasy? Hepatology, 2006, 43 (2 Suppl 1), s. 82–88.

9. Friedman, S. L. Mechanisms of disease: Mechanisms of hepatic fibrosis and therapeutic implications. Nat. Clin. Pract. Gastroenterol. Hepatol., 2004, 1, s. 98–105.

10. Friedman, S. L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem., 2000, 275, 4, s. 2247–2250.

11. Gaca, M. D., Zhou, X., Issa, R. et al. Basement membrane-like matrix inhibits proliferation and collagen synthesis by activated rat hepatic stellate cells: evidence for matrix-dependent deactivation of stellate cells. Matrix Biol., 2003, 22, s. 229–239.

12. Geerts, A. History, heterogeneity, developmental biology, and functions of quiescent hepaticstellate cells. Semin. Liver Dis., 2001, 21, s. 311–335.

13. Habens, F., Srinivasan, N., Oakley, F. et al. Novel sulfasalazine analogues with enhanced NF-kB inhibitory and apoptosis promoting activity. Apoptosis, 2005, 10, s. 481–491.

14. Han, Y. P., Zhou, L., Wang, J., Xiong, S., Garner, W. L., French, S. W., Tsukamoto, H. Essential role of matrix metalloproteinases in interleukin-1-induced myofibroblastic activation of hepatic stellate cell in collagen. J. Biol. Chem., 2004, 6, 279, 6, s. 4820-8. Epub 2003 Nov 14.

15. Chor, S. Y., Hui, A. Y., To, K. F., Chan, K. K., Go, Y. Y., Chan, H. L., Leung, W. K., Sung, J. J. Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic stellate cell. J. Ethnopharmacol., 2005, 100, 1–2), s. 180–186.

16. Iredale, J. P. Hepatic stellate cell behavior during resolution of liver injury. Semin. Liver Dis., 2001, 3, s. 427–-36.

17. Iredale, J. P., Benyon, R. C., Pickering, J., McCullen, M., Northrop, M., Pawley, S. et al. Mechanisms of spontaneous resolution of rat liver fibrosis: hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J. Clin. Invest., 1998, s. 538–549.

18. Issa, R., Zhou, X., Constandinou, C. M., Fallowfield, J., Millward-Sadler, H., Gaca, M. D., Sands, E., Suliman, I., Trim, N., Knorr, A., Arthur, M. J., Benyon, R. C., Iredale, J. P. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology, 2004, 126, s. 1795–1808.

19. Ji, G., Wang, L., Zhang, S. H., Liu, J. W., Zheng, P. Y., Liu, T. Effect of Chinese medicine Qinggan Huoxuefang on inducing HSC apoptosis in alcoholic liver fibrosis rats. World J. Gastroenterol., 2006, 12, 13, s. 2047–2052.

20. Kisseleva, T., Brenner, D. Stellate Cell Biology. Hepatic stellate cells and the reversal of fibrosis. J. Gastroenterol. Hepat., 2006, 21, s. 84–87.

21. Lin, H. J., Tseng, C. P., Lin, C. F., Liao, M. H., Chen, C. M., Kao, S. T., Cheng, J. C. A Chinese Herbal Decoction, Modified Yi Guan Jian, Induces Apoptosis in Hepatic Stellate Cells through an ROS-Mediated Mitochondrial/Caspase Pathway. Evid. Based Complement. Alternat. Med., 2011, 459531. Epub 2010 Sep 26.

22. Lotersztajn, S., Julien, B., Teixeira-Clerc, F., Grenard, P., Mallat, A. Hepatic fibrosis: Molecular mechanisms and drug targets. Annual Review of Pharmacology and Toxicology, 2005, 45, s. 605–628.

23. Montiel-Duarte, C., Varela-Rey, M., Oses-Prieto, J. A., Lopez-Zabalza, M. J., Beitia, G., Cenarruzabeitia, E., Iraburu, M. J. 3,4-Methylenedioxymethamphetamine ("Ecstasy") induces apoptosis of cultured rat liver cells. Biochim. Biophys. Acta, 2002, 1588, 1, s. 26–32.

24. Murphy, F. R., Issa, R., Zhou, X., Ratnarajah, S., Nagase, H., Arthur, M. J., Benyon, C., Iredale, J. P. Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis. J. Biol. Chem., 2002, 277, s. 11069–11076.

25. Muddu, A. K., Guha, I. N., Elsharkawy, A. M., Mann, D. A. Resolving fibrosis in the disased liver:Translating the scientific promise to the clinic. Int. J. Biochem. Cell Biol., 2007, 39, 4, s. 695–714, Epub 2006 Oct 7.

26. Oakley, F., Meso, M., Iredale, J. P. et al. Inhibition of nB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology, 2005, 128, s. 108–120.

27. Olaso, E., Ikeda, K., Eng, F. J. et al. DDR2 receptor MMP-2-mediated proliferation and invasion by hepatic stellate cells. J. Clin. Invest., 2001, 108, s. 1369–1378.

28. Orr, J. G., Leel, V., Cameron, G. A., Marek, C. J., Haughton, E. L., Elrick, L. J. et al. Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells. Hepatology, 2004, 40, s. 232–242.

29. Pelclová, D., Lebedová, J. Nemoci z povolání a intoxikace. Praha: Karolinum 2002, s. 111–114.

30. Sarem, M., Znaidak, R., Macias, M., Rey, R. Hepatic stellate cells: it’s role in normal and pathological conditions. Gastroenterol. Hepatol., 2006 Feb;29(2):93-101.

31. Sato, M., Suzuki, S., Senoo, H. Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct., 2003, s. 105–112, review.

32. Senoo, H., Hata, R. Extracellular matrix regulates cell morphology, proliferation, and tissue formation. Kaibogaku Zasshi, 1994, 69, 6, s. 719–733.

33. Schuppan, D. Structure of extracellular matrix in normal and fibrotic liver:collagens and glycoproteins. Semin. Liver Dis., 1990, s. 1–10.

34. Sohara, N., Znoyko, I., Levy, M. T., Trojanowska, M., Reuben, A. Reversal of activation of human myofibroblast-like cells by culture on a basement membrane-like substrate. Journal of Hepatology, 2002, 37, 2, s. 214–221.

35. Taimr, P., Higuchi, H., Kocova, E., Rippe, R. A., Friedman, S., Gores, G. J. Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo TRAIL-mediated apoptosis. Hepatology, 2003, 37, 1, s. 87–95.

36. Tsukada, S., Parsons, C. J., Rippe, R. A. Mechanisms of liver fibrosis. Clin. Chim. Acta, 2006, 64, 1–2, 33-60. Epub 2005 Sep 1.

37. Wright, M. C., Issa, R., Smart, D. E., Trim, N., Murray, G. I., Primrose, J. N. et al. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology, 2001, 121, s. 685–698.

38. Yao, X. X., Tang, Y. W., Yao, D. M., Xiu, H. M. Effects of Yigan Decoction on proliferation and apoptosis of hepatic stellate cells. World J. Gastroenterol., 2002, 8, 3, s. 511–514.

39. Zhang, B. J., Xu, D., Guo, Y., Ping, J., Chen, L. B., Wang, H. Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors. Clin. Exp. Pharmacol. Physiol., 2008, 3, s. 303–309.

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