Молекулярные факторы, ассоциированные с регрессом фиброза печени алкогольной этиологии
Терапевтический архив. 2021; 93 (2): 204–208. DOI: 10.26442/00403660.2021.02.200617
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Kiseleva Ya.V., Zharikov Yu.O., Maslennikov R.V., et al. Molecular factors associated with regression of liver fibrosis of alcoholic etiology. Terapevticheskii Arkhiv (Ter. Arkh.). 2021; 93 (2): 204–208. DOI: 10.26442/00403660.2021.02.200617
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Ключевые слова: фиброз печени, алкогольная болезнь печени, патогенез, молекулярные пути регресса
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Liver fibrosis develops as a result of chronic liver damage of various etiologies, is characterized by excessive synthesis of connective tissue by activated stellate liver cells. The toxic effect of alcohol is one of the most significant and common etiological factors worldwide. Stellate cell activation results from the interaction of multiple molecular fibrogenic pathways triggered by intracellular and extracellular, hepatic and extrahepatic stimuli. Data analysis showed that knowledge about these abnormal pathways and biomolecular processes may further contribute to the improvement of approaches to assessment of disease prognosis and treatment of alcoholic liver disease.
Keywords: liver fibrosis, alcoholic liver disease, pathogenesis, molecular pathways of regression
2. Weiskirchen R, Tacke F. Liver Fibrosis: Fr om Pathogenesis to Novel Therapies. Dig Dis. 2016;34(4):410-22. doi: 10.1159/000444556
3. Zhang CY, Yuan WG, He P, et al. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic argets. World J Gastroenterol. 2016;22(48):10512-22. doi: 10.3748/wjg.v22.i48.10512
4. Lee YA, Wallace MC, Friedman SL. Pathobiology of liver fibrosis: a translational success story. Gut. 2015;64(5):830-41. doi: 10.1136/gutjnl-2014-30684
5. Aydın MM, Akçalı KC. Liver fibrosis. Turk J Gastroenterol. 2018;29(1):14-21. doi: 10.5152/tjg.2018.17330
6. Zoubek ME, Trautwein C, Strnad P. Reversal of liver fibrosis: From fiction to reality. Best Pract Res Clin Gastroenteroly. 2017;31(2):129-41. doi: 10.1016/j.bpg.2017.04.005
7. Ramachandran P, Iredale JP, Fallowfield JA. Resolution of liver fibrosis: basic mechanisms and clinical relevance. Semin Liver Dis. 2015;35(2):119-31. doi: 10.1055/s-0035-1550057
8. Moscoso CG, Steer CJ. “Let my liver rather heat with wine” – a review of hepatic fibrosis pathophysiology and emerging therapeutics. Hepat Med. 2019;11:109-29. doi: 10.2147/HMER.S213397
9. Huang Y, Deng X, Liang J. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis. Exp Cell Res. 2017;352(2):420-6. doi: 10.1016/j.yexcr.2017.02.038
10. Feng M, Ding J, Wang M, et al. Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution. Int J Biol Sci. 2018;14(9):1033-40. doi: 10.7150/ijbs.25589
11. Faggioli F, Palagano E, Di Tommaso L, et al. B lymphocytes lim it senescence-driven fibrosis resolution and favor hepatocarcinogenesis in mouse liver injury. Hepatology. 2018;67(5):1970-85. doi: 10.1002/hep.29636
12. Atta HM. Reversibility and heritability of liver fibrosis: Implications for research and therapy. World J Gastroenterol. 2015;21(17):5138-48. doi: 10.3748/wjg.v21.i17.5138
13. Jung YK, Yim HJ. Reversal of liver cirrhosis: current evidence and expectations. Korean J Intern Med. 2017;32(2):213-28. doi: 10.3904/kjim.2016.268
14. Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: Direct antifibrotic agents and targeted therapies. Matrix Biol. 2018;68-69:435-51. doi: 10.1016/j.matbio.2018.04.006
15. Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol. 2017;66(6):1300-12. doi: 10.1016/j.jhep.2017.02.026
16. Tacke F, Weiskirchen R. An update on the recent advances in antifibrotic therapy. Expert Rev Gastroenterol Hepatol. 2018;12(11):1143-52. doi: 10.1080/17474124.2018.1530110
17. Weiskirchen R, Tacke F. Liver Fibrosis: From Pathogenesis to Novel Therapies. Dig Dis. 2016;34(4):410-22. doi: 10.1159/000444556
18. Mridha AR, Wree A, Robertson AAB, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J Hepatol. 2017;66(5):1037-46. doi: 10.1016/j.jhep.2017.01.022
19. Omar R, Yang J, Liu H, et al. Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy. Rev Physiol Biochem Pharmacol. 2016;172:1-37. doi: 10.1007/112_2016_6
20. Calvente CJ, Tameda M, Johnson CD, et al. Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223. J Clin Invest. 2019;130:4091-109. doi: 10.1172/JCI122258
21. Saijou E, Enomoto Y, Matsuda M, et al. Neutrophils alleviate fibrosis in the CCl4-induced mouse chronic liver injury model. Hepatol Commun. 2018;2(6):703-17. doi: 10.1002/hep4.1178
22. Ye D, Zhang T, Lou G, Liu Y. Role of miR-223 in the pathophysiology of liver diseases. Exp Mol Med. 2018;50(9):128. doi: 10.1038/s12276-018-0153-7
23. Tsay HC, Yuan Q, Balakrishnan A, et al. Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis. J Hepatol. 2019;70(4):722-34. doi: 10.1016/j.jhep.2018.12.016
24. Newsome PN, Fox R, King AL, et al. Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2018;3(1):25-36. doi: 10.1016/S2468-1253(17)30326-6
25. Park S, Kim JW, Kim JH, et al. Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver. Biol Pharm Bull. 2015;38(7):980-5. doi: 10.1248/bpb.b15-00325
26. Leake I. Liver: Does angiogenesis have a role in the resolution of liver fibrosis? Nat Rev Gastroenterol Hepatol. 2015;12(2):63. doi: 10.1038/nrgastro.2014.230
27. Kantari-Mimoun C, Krzywinska E, Castells M, et al. Boosting the hypoxic response in myeloid cells accelerates resolution of fibrosis and regeneration of the liver in mice. Oncotarget. 2017;8(9):15085-100. doi: 10.18632/oncotarget.14749
28. Lee HS, Choi J, Son T, et al. Altered AKAP12 expression in portal fibroblasts and liver sinusoids mediates transition from hepatic fibrogenesis to fibrosis resolution. Exp Mol Med. 2018;50(4):48.
doi: 10.1038/s12276-018-0074-5
29. Chen L, Brenner DA, Kisseleva T. Combatting Fibrosis: Exosome-Based Therapies in the Regression of Liver Fibrosis. Hepatology Commun. 2018;3(2):180-92. doi: 10.1002/hep4.1290
30. Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomedicine. 2017;12:6997-7006. doi: 10.2147/IJN.S145951
31. Bartneck M, Scheyda KM, Warzecha KT, et al. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials. 2015;37:367-82.
doi: 10.1016/j.biomaterials.2014.10.030
32. Caliari SR, Perepelyuk M, Soulas EM, et al. Gradually softening hydrogels for modeling hepatic stellate cell behavior during fibrosis regression. Integr Biol (Camb.). 2016;8(6):720-8. doi: 10.1039/c6ib00027d
33. Sumida Y, Okanoue T, Nakajima A; Japan Study Group of NAFLD (JSG-NAFLD). Phase 3 drug pipelines in the treatment of non-alcoholic steatohepatitis. Hepatology Res. 2019. doi: 10.1111/hepr.13425
34. Ratziu V, Harrison SA, Francque S, et al. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology. 2016;150(5):1147-59.e5. doi: 10.1053/j.gastro.2016.01.038
35. Kumar V, Mahato RI. Delivery and targeting of miRNAs for treating liver fibrosis. Pharmaceutical Res. 2015;32(2):341-61. doi: 10.1007/s11095-014-1497-x
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1. Sun M, Kisseleva T. Reversibility of liver fibrosis. Clin Res Hepatol Gastroenterol. 2015;39 Suppl. 1:S60-3. doi: 10.1016/j.clinre.2015.06.015
2. Weiskirchen R, Tacke F. Liver Fibrosis: Fr om Pathogenesis to Novel Therapies. Dig Dis. 2016;34(4):410-22. doi: 10.1159/000444556
3. Zhang CY, Yuan WG, He P, et al. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic argets. World J Gastroenterol. 2016;22(48):10512-22. doi: 10.3748/wjg.v22.i48.10512
4. Lee YA, Wallace MC, Friedman SL. Pathobiology of liver fibrosis: a translational success story. Gut. 2015;64(5):830-41. doi: 10.1136/gutjnl-2014-30684
5. Aydın MM, Akçalı KC. Liver fibrosis. Turk J Gastroenterol. 2018;29(1):14-21. doi: 10.5152/tjg.2018.17330
6. Zoubek ME, Trautwein C, Strnad P. Reversal of liver fibrosis: From fiction to reality. Best Pract Res Clin Gastroenteroly. 2017;31(2):129-41. doi: 10.1016/j.bpg.2017.04.005
7. Ramachandran P, Iredale JP, Fallowfield JA. Resolution of liver fibrosis: basic mechanisms and clinical relevance. Semin Liver Dis. 2015;35(2):119-31. doi: 10.1055/s-0035-1550057
8. Moscoso CG, Steer CJ. “Let my liver rather heat with wine” – a review of hepatic fibrosis pathophysiology and emerging therapeutics. Hepat Med. 2019;11:109-29. doi: 10.2147/HMER.S213397
9. Huang Y, Deng X, Liang J. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis. Exp Cell Res. 2017;352(2):420-6. doi: 10.1016/j.yexcr.2017.02.038
10. Feng M, Ding J, Wang M, et al. Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution. Int J Biol Sci. 2018;14(9):1033-40. doi: 10.7150/ijbs.25589
11. Faggioli F, Palagano E, Di Tommaso L, et al. B lymphocytes lim it senescence-driven fibrosis resolution and favor hepatocarcinogenesis in mouse liver injury. Hepatology. 2018;67(5):1970-85. doi: 10.1002/hep.29636
12. Atta HM. Reversibility and heritability of liver fibrosis: Implications for research and therapy. World J Gastroenterol. 2015;21(17):5138-48. doi: 10.3748/wjg.v21.i17.5138
13. Jung YK, Yim HJ. Reversal of liver cirrhosis: current evidence and expectations. Korean J Intern Med. 2017;32(2):213-28. doi: 10.3904/kjim.2016.268
14. Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: Direct antifibrotic agents and targeted therapies. Matrix Biol. 2018;68-69:435-51. doi: 10.1016/j.matbio.2018.04.006
15. Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol. 2017;66(6):1300-12. doi: 10.1016/j.jhep.2017.02.026
16. Tacke F, Weiskirchen R. An update on the recent advances in antifibrotic therapy. Expert Rev Gastroenterol Hepatol. 2018;12(11):1143-52. doi: 10.1080/17474124.2018.1530110
17. Weiskirchen R, Tacke F. Liver Fibrosis: From Pathogenesis to Novel Therapies. Dig Dis. 2016;34(4):410-22. doi: 10.1159/000444556
18. Mridha AR, Wree A, Robertson AAB, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J Hepatol. 2017;66(5):1037-46. doi: 10.1016/j.jhep.2017.01.022
19. Omar R, Yang J, Liu H, et al. Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy. Rev Physiol Biochem Pharmacol. 2016;172:1-37. doi: 10.1007/112_2016_6
20. Calvente CJ, Tameda M, Johnson CD, et al. Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223. J Clin Invest. 2019;130:4091-109. doi: 10.1172/JCI122258
21. Saijou E, Enomoto Y, Matsuda M, et al. Neutrophils alleviate fibrosis in the CCl4-induced mouse chronic liver injury model. Hepatol Commun. 2018;2(6):703-17. doi: 10.1002/hep4.1178
22. Ye D, Zhang T, Lou G, Liu Y. Role of miR-223 in the pathophysiology of liver diseases. Exp Mol Med. 2018;50(9):128. doi: 10.1038/s12276-018-0153-7
23. Tsay HC, Yuan Q, Balakrishnan A, et al. Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis. J Hepatol. 2019;70(4):722-34. doi: 10.1016/j.jhep.2018.12.016
24. Newsome PN, Fox R, King AL, et al. Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2018;3(1):25-36. doi: 10.1016/S2468-1253(17)30326-6
25. Park S, Kim JW, Kim JH, et al. Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver. Biol Pharm Bull. 2015;38(7):980-5. doi: 10.1248/bpb.b15-00325
26. Leake I. Liver: Does angiogenesis have a role in the resolution of liver fibrosis? Nat Rev Gastroenterol Hepatol. 2015;12(2):63. doi: 10.1038/nrgastro.2014.230
27. Kantari-Mimoun C, Krzywinska E, Castells M, et al. Boosting the hypoxic response in myeloid cells accelerates resolution of fibrosis and regeneration of the liver in mice. Oncotarget. 2017;8(9):15085-100. doi: 10.18632/oncotarget.14749
28. Lee HS, Choi J, Son T, et al. Altered AKAP12 expression in portal fibroblasts and liver sinusoids mediates transition from hepatic fibrogenesis to fibrosis resolution. Exp Mol Med. 2018;50(4):48.
doi: 10.1038/s12276-018-0074-5
29. Chen L, Brenner DA, Kisseleva T. Combatting Fibrosis: Exosome-Based Therapies in the Regression of Liver Fibrosis. Hepatology Commun. 2018;3(2):180-92. doi: 10.1002/hep4.1290
30. Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomedicine. 2017;12:6997-7006. doi: 10.2147/IJN.S145951
31. Bartneck M, Scheyda KM, Warzecha KT, et al. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials. 2015;37:367-82.
doi: 10.1016/j.biomaterials.2014.10.030
32. Caliari SR, Perepelyuk M, Soulas EM, et al. Gradually softening hydrogels for modeling hepatic stellate cell behavior during fibrosis regression. Integr Biol (Camb.). 2016;8(6):720-8. doi: 10.1039/c6ib00027d
33. Sumida Y, Okanoue T, Nakajima A; Japan Study Group of NAFLD (JSG-NAFLD). Phase 3 drug pipelines in the treatment of non-alcoholic steatohepatitis. Hepatology Res. 2019. doi: 10.1111/hepr.13425
34. Ratziu V, Harrison SA, Francque S, et al. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology. 2016;150(5):1147-59.e5. doi: 10.1053/j.gastro.2016.01.038
35. Kumar V, Mahato RI. Delivery and targeting of miRNAs for treating liver fibrosis. Pharmaceutical Res. 2015;32(2):341-61. doi: 10.1007/s11095-014-1497-x
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия
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Ya.V. Kiseleva1, Yu.O. Zharikov1, R.V. Maslennikov1, Ch.S. Pavlov1, V.N. Nikolenko1,2
1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2 Lomonosov Moscow State University, Moscow, Russia