Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver


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Background:The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.

Aim:This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.

Methods:After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.

Results:Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.

Conclusion:Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

Sobre autores

Vasilii Slautin

Department of Pathophysiology, Ural State Medical University

Autor responsável pela correspondência
Email: info@benthamscience.net

Konstantin Konyshev

Department of Pathophysiology, Ural State Medical University

Email: info@benthamscience.net

Ilya Gavrilov

Department of Pathophysiology, Ural State Medical University

Email: info@benthamscience.net

Olga Beresneva

Department of Pathophysiology, Ural State Medical University

Email: info@benthamscience.net

Irina Maklakova

Department of Pathophysiology, Ural State Medical University

Email: info@benthamscience.net

Dmitry Grebnev

Department of Pathophysiology, Ural State Medical University

Email: info@benthamscience.net

Bibliografia

  1. Wang, J.; Chen, Z.; Sun, M.; Xu, H.; Gao, Y.; Liu, J.; Li, M. Characterization and therapeutic applications of mesenchymal stem cells for regenerative medicine. Tissue Cell, 2020, 64, 101330. doi: 10.1016/j.tice.2020.101330 PMID: 32473704
  2. Cardinale, V.; Lanthier, N.; Baptista, P.M.; Carpino, G.; Carnevale, G.; Orlando, G.; Angelico, R.; Manzia, T.M.; Schuppan, D.; Pinzani, M.; Alvaro, D.; Ciccocioppo, R.; Uygun, B.E. Cell transplantation-based regenerative medicine in liver diseases. Stem Cell Reports, 2023, 18(8), 1555-1572. doi: 10.1016/j.stemcr.2023.06.005 PMID: 37557073
  3. Mahjoor, M.; Fakouri, A.; Farokhi, S.; Nazari, H.; Afkhami, H.; Heidari, F. Regenerative potential of mesenchymal stromal cells in wound healing: unveiling the influence of normoxic and hypoxic environments. Front. Cell Dev. Biol., 2023, 11, 1245872. doi: 10.3389/fcell.2023.1245872 PMID: 37900276
  4. Lou, S.; Duan, Y.; Nie, H.; Cui, X.; Du, J.; Yao, Y. Mesenchymal stem cells: Biological characteristics and application in disease therapy. Biochimie, 2021, 185, 9-21. doi: 10.1016/j.biochi.2021.03.003 PMID: 33711361
  5. Liu, P.; Qian, Y.; Liu, X.; Zhu, X.; Zhang, X.; Lv, Y.; Xiang, J. Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis. Front. Immunol., 2023, 13, 1096402. doi: 10.3389/fimmu.2022.1096402 PMID: 36685534
  6. Liu, P.; Mao, Y.; Xie, Y.; Wei, J.; Yao, J. Stem cells for treatment of liver fibrosis/cirrhosis: Clinical progress and therapeutic potential. Stem Cell Res. Ther., 2022, 13(1), 356. doi: 10.1186/s13287-022-03041-5 PMID: 35883127
  7. Yao, L.; Hu, X.; Dai, K.; Yuan, M.; Liu, P.; Zhang, Q.; Jiang, Y. Mesenchymal stromal cells: Promising treatment for liver cirrhosis. Stem Cell Res. Ther., 2022, 13(1), 308. doi: 10.1186/s13287-022-03001-z PMID: 35841079
  8. Hu, X.; Ge, Q.; Zhang, Y.; Li, B.; Cheng, E.; Wang, Y.; Huang, Y. A review of the effect of exosomes from different cells on liver fibrosis. Biomed. Pharmacother., 2023, 161, 114415. doi: 10.1016/j.biopha.2023.114415 PMID: 36812711
  9. Jones, B.; Li, C.; Park, M.S.; Lerch, A.; Jacob, V.; Johnson, N.; Kuang, J.Q.; Dhall, S.; Sathyamoorthy, M. Comprehensive comparison of amnion stromal cells and chorion stromal cells by RNA-seq. Int. J. Mol. Sci., 2021, 22(4), 1901. doi: 10.3390/ijms22041901 PMID: 33672986
  10. Chen, L.; Merkhan, M.M.; Forsyth, N.R.; Wu, P. Chorionic and amniotic membrane-derived stem cells have distinct, and gestational diabetes mellitus independent, proliferative, differentiation, and immunomodulatory capacities. Stem Cell Res., 2019, 40, 101537. doi: 10.1016/j.scr.2019.101537 PMID: 31422237
  11. Jeon, Y.J.; Kim, J.; Cho, J.H.; Chung, H.M.; Chae, J.I. Comparative analysis of human mesenchymal stem cells derived from bone marrow, placenta, and adipose tissue as sources of cell therapy. J. Cell. Biochem., 2016, 117(5), 1112-1125. doi: 10.1002/jcb.25395 PMID: 26448537
  12. Zhang, Y.; Ravikumar, M.; Ling, L.; Nurcombe, V.; Cool, S.M. Age-related changes in the inflammatory status of human mesenchymal stem cells: implications for cell therapy. Stem Cell Reports, 2021, 16(4), 694-707. doi: 10.1016/j.stemcr.2021.01.021 PMID: 33636113
  13. Gao, Y.; Chi, Y.; Chen, Y.; Wang, W.; Li, H.; Zheng, W.; Zhu, P.; An, J.; Duan, Y.; Sun, T.; Liu, X.; Xue, F.; Liu, W.; Fu, R.; Han, Z.; Zhang, Y.; Yang, R.; Cheng, T.; Wei, J.; Zhang, L.; Zhang, X. Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1. Nat. Commun., 2023, 14(1), 4373. doi: 10.1038/s41467-023-39958-5 PMID: 37474525
  14. Torre, P.; Flores, A.I. Current status and future prospects of perinatal stem cells. Genes, 2020, 12(1), 6. doi: 10.3390/genes12010006 PMID: 33374593
  15. Yao, Q.; Chen, W.; Yu, Y.; Gao, F.; Zhou, J.; Wu, J.; Pan, Q.; Yang, J.; Zhou, L.; Yu, J.; Cao, H.; Li, L. Human placental mesenchymal stem cells relieve primary sclerosing cholangitis via upregulation of TGR5 in Mdr2 −/− mice and human intrahepatic cholangiocyte organoid models. Research, 2023, 6, 0207. doi: 10.34133/research.0207 PMID: 37600495
  16. Li, S.; Wang, J.; Jiang, B.; Jiang, J.; Luo, L.; Zheng, B.; Si, W. Mesenchymal stem cells derived from different perinatal tissues donated by same donors manifest variant performance on the acute liver failure model in mouse. Stem Cell Res. Ther., 2022, 13(1), 231. doi: 10.1186/s13287-022-02909-w PMID: 35659084
  17. Kim, S.H.; Kim, J.Y.; Park, S.Y.; Jeong, W.T.; Kim, J.M.; Bae, S.H.; Kim, G.J. Activation of the EGFR-PI3K- CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium. Stem Cell Res. Ther., 2021, 12(1), 551. doi: 10.1186/s13287-021-02616-y PMID: 34689832
  18. Na, J.; Song, J.; Kim, H.H.; Seok, J.; Kim, J.Y.; Jun, J.H.; Kim, G.J. Human placenta-derived mesenchymal stem cells trigger repair system in TAA-injured rat model via antioxidant effect. Aging, 2021, 13(1), 61-76. doi: 10.18632/aging.202348 PMID: 33406506
  19. Yao, Y.; Xia, Z.; Cheng, F.; Jang, Q.; He, J.; Pan, C.; Zhang, L.; Ye, Y.; Wang, Y.; Chen, S.; Su, D.; Su, X.; Cheng, L.; Shi, G.; Dai, L.; Deng, H. Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin1 in hepatic stellate cells. Stem Cell Res. Ther., 2021, 12(1), 294. doi: 10.1186/s13287-021-02358-x PMID: 34016164
  20. Slautin, V.N.; Grebnev, D.Y.; Maklakova, I.Y.; Sazonov, S.V. Fucoxanthin exert dose-dependent antifibrotic and anti-inflammatory effects on CCl4-induced liver fibrosis. J. Nat. Med., 2023, 77(4), 953-963. doi: 10.1007/s11418-023-01723-9 PMID: 37391684
  21. Mumu, M.; Das, A.; Emran, T.B.; Mitra, S.; Islam, F.; Roy, A.; Karim, M.M.; Das, R.; Park, M.N.; Chandran, D.; Sharma, R.; Khandaker, M.U.; Idris, A.M.; Kim, B. Fucoxanthin: A promising phytochemical on diverse pharmacological targets. Front. Pharmacol., 2022, 13, 929442. doi: 10.3389/fphar.2022.929442 PMID: 35983376
  22. Bae, M.; Kim, M.B.; Park, Y.K.; Lee, J.Y. Health benefits of fucoxanthin in the prevention of chronic diseases. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2020, 1865(11), 158618. doi: 10.1016/j.bbalip.2020.158618 PMID: 31931174
  23. Li, N.; Gao, X.; Zheng, L.; Huang, Q.; Zeng, F.; Chen, H.; Farag, M.A.; Zhao, C. Advances in fucoxanthin chemistry and management of neurodegenerative diseases. Phytomedicine, 2022, 105, 154352. doi: 10.1016/j.phymed.2022.154352 PMID: 35917771
  24. Miyashita, K.; Hosokawa, M. Fucoxanthin in the management of obesity and its related disorders. J. Funct. Foods, 2017, 36, 195-202. doi: 10.1016/j.jff.2017.07.009
  25. Winarto, J.; Song, D.G.; Pan, C.H. The role of fucoxanthin in non-alcoholic fatty liver disease. Int. J. Mol. Sci., 2023, 24(9), 8203. doi: 10.3390/ijms24098203 PMID: 37175909
  26. Guan, B.; Chen, K.; Tong, Z.; Chen, L.; Chen, Q.; Su, J. Advances in fucoxanthin research for the prevention and treatment of inflammation-related diseases. Nutrients, 2022, 14(22), 4768. doi: 10.3390/nu14224768 PMID: 36432455
  27. Liu, M.; Li, W.; Chen, Y.; Wan, X.; Wang, J. Fucoxanthin: A promising compound for human inflammation-related diseases. Life Sci., 2020, 255, 117850. doi: 10.1016/j.lfs.2020.117850 PMID: 32470447
  28. Li, S.; Ren, X.; Wang, Y.; Hu, J.; Wu, H.; Song, S.; Yan, C. Fucoxanthin alleviates palmitate-induced inflammation in RAW 264.7 cells through improving lipid metabolism and attenuating mitochondrial dysfunction. Food Funct., 2020, 11(4), 3361-3370. doi: 10.1039/D0FO00442A PMID: 32232236
  29. Jeong, S.; Kim, M.B.; Baek, S.; Lee, J.; Lee, H.; Cao, B.; Kim, Y.; Cao, L.; Lee, S. Suppression of pro-inflammatory M1 polarization of LPS-stimulated RAW 264.7 macrophage cells by fucoxanthin-rich sargassum hemiphyllum. Mar. Drugs, 2023, 21(10), 533. doi: 10.3390/md21100533 PMID: 37888467
  30. Ben Ammar, R.; Zahra, H.A.; Abu Zahra, A.M.; Alfwuaires, M.; Abdulaziz Alamer, S.; Metwally, A.M.; Althnaian, T.A.; Al-Ramadan, S.Y. Protective effect of fucoxanthin on zearalenone-induced hepatic damage through Nrf2 mediated by PI3K/AKT signaling. Mar. Drugs, 2023, 21(7), 391. doi: 10.3390/md21070391 PMID: 37504922
  31. Kim, M.B.; Bae, M.; Hu, S.; Kang, H.; Park, Y.K.; Lee, J.Y. Fucoxanthin exerts anti-fibrogenic effects in hepatic stellate cells. Biochem. Biophys. Res. Commun., 2019, 513(3), 657-662. doi: 10.1016/j.bbrc.2019.04.052 PMID: 30982574
  32. Li, Y.; Kim, M.B.; Park, Y.K.; Lee, J.Y. Fucoxanthin metabolites exert anti-fibrogenic and antioxidant effects in hepatic stellate cells. J. Agricult. Food Res., 2021, 6, 100245. doi: 10.1016/j.jafr.2021.100245
  33. Takatani, N.; Kono, Y.; Beppu, F.; Okamatsu-Ogura, Y.; Yamano, Y.; Miyashita, K.; Hosokawa, M. Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice. Biochem. Biophys. Res. Commun., 2020, 528(2), 305-310. doi: 10.1016/j.bbrc.2020.05.050 PMID: 32475638
  34. Nan, Y.; Su, H.; Lian, X.; Wu, J.; Liu, S.; Chen, P.; Liu, S. Pathogenesis of liver fibrosis and its TCM therapeutic perspectives. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-12. doi: 10.1155/2022/5325431 PMID: 35529927
  35. Zhang, C.Y.; Liu, S.; Yang, M. Treatment of liver fibrosis: Past, current, and future. World J. Hepatol., 2023, 15(6), 755-774. doi: 10.4254/wjh.v15.i6.755 PMID: 37397931
  36. Liu, Y.B.; Chen, M.K. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J. Gastroenterol., 2022, 28(41), 5910-5930. doi: 10.3748/wjg.v28.i41.5910 PMID: 36405106
  37. Zanetto, A.; Shalaby, S.; Gambato, M.; Germani, G.; Senzolo, M.; Bizzaro, D.; Russo, F.P.; Burra, P. New indications for liver transplantation. J. Clin. Med., 2021, 10(17), 3867. doi: 10.3390/jcm10173867 PMID: 34501314
  38. Ngu, N.L.Y.; Flanagan, E.; Bell, S.; Le, S.T. Acute-on-chronic liver failure: Controversies and consensus. World J. Gastroenterol., 2023, 29(2), 232-240. doi: 10.3748/wjg.v29.i2.232 PMID: 36687118
  39. Karvellas, C.J.; Francoz, C.; Weiss, E. Liver transplantation in acute-on-chronic liver failure. Transplantation, 2021, 105(7), 1471-1481. doi: 10.1097/TP.0000000000003550 PMID: 33208692
  40. Huang, Q.; Yang, Y.; Luo, C.; Wen, Y.; Liu, R.; Li, S.; Chen, T.; Sun, H.; Tang, L. An efficient protocol to generate placental chorionic plate-derived mesenchymal stem cells with superior proliferative and immunomodulatory properties. Stem Cell Res. Ther., 2019, 10(1), 301. doi: 10.1186/s13287-019-1405-8 PMID: 31623677
  41. Nallagangula, K.S.; Nagaraj, S.K.; Venkataswamy, L.; Chandrappa, M. Liver fibrosis: A compilation on the biomarkers status and their significance during disease progression. Future Sci. OA, 2018, 4(1), FSO250. doi: 10.4155/fsoa-2017-0083 PMID: 29255622
  42. Sharma, P. Value of liver function tests in cirrhosis. J. Clin. Exp. Hepatol., 2022, 12(3), 948-964. doi: 10.1016/j.jceh.2021.11.004 PMID: 35677506
  43. Ong, C.H.; Tham, C.L.; Harith, H.H.; Firdaus, N.; Israf, D.A. TGF-β-induced fibrosis: A review on the underlying mechanism and potential therapeutic strategies. Eur. J. Pharmacol., 2021, 911, 174510. doi: 10.1016/j.ejphar.2021.174510 PMID: 34560077
  44. Gough, N.R.; Xiang, X.; Mishra, L. TGF-β signaling in liver, pancreas, and gastrointestinal diseases and cancer. Gastroenterology, 2021, 161(2), 434-452.e15. doi: 10.1053/j.gastro.2021.04.064 PMID: 33940008
  45. Lee, Y-S.; Seki, E. In vivo and in vitro models to study liver fibrosis: Mechanisms and limitations. Cell Mol. Gastroenterol. Hepatol., 2023, 100788. doi: 10.1016/j.jcmgh.2023.05.010
  46. Wu, S.; Wang, X.; Xing, W.; Li, F.; Liang, M.; Li, K.; He, Y.; Wang, J. An update on animal models of liver fibrosis. Front. Med., 2023, 10, 1160053. doi: 10.3389/fmed.2023.1160053 PMID: 37035335
  47. Akdis, M.; Aab, A.; Altunbulakli, C.; Azkur, K.; Costa, R.A.; Crameri, R.; Duan, S.; Eiwegger, T.; Eljaszewicz, A.; Ferstl, R.; Frei, R.; Garbani, M.; Globinska, A.; Hess, L.; Huitema, C.; Kubo, T.; Komlosi, Z.; Konieczna, P.; Kovacs, N.; Kucuksezer, U.C.; Meyer, N.; Morita, H.; Olzhausen, J.; O’Mahony, L.; Pezer, M.; Prati, M.; Rebane, A.; Rhyner, C.; Rinaldi, A.; Sokolowska, M.; Stanic, B.; Sugita, K.; Treis, A.; van de Veen, W.; Wanke, K.; Wawrzyniak, M.; Wawrzyniak, P.; Wirz, O.F.; Zakzuk, J.S.; Akdis, C.A. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J. Allergy Clin. Immunol., 2016, 138(4), 984-1010. doi: 10.1016/j.jaci.2016.06.033 PMID: 27577879
  48. Sabir U, Gu HM, Zhang DW. Extracellular matrix turnover: Phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis. Phytother Res 2023; 37(11): 4932-4962. doi: 10.1002/ptr.7959
  49. Khurana, A.; Sayed, N.; Allawadhi, P.; Weiskirchen, R. It’s all about the spaces between cells: Role of extracellular matrix in liver fibrosis. Ann. Transl. Med., 2021, 9(8), 728-728. doi: 10.21037/atm-20-2948 PMID: 33987426
  50. Molière, S.; Jaulin, A.; Tomasetto, C.L.; Dali-Youcef, N. Roles of matrix metalloproteinases and their natural inhibitors in metabolism: Insights into health and disease. Int. J. Mol. Sci., 2023, 24(13), 10649. doi: 10.3390/ijms241310649 PMID: 37445827
  51. Lu, W.; Qu, J.; Yan, L.; Tang, X.; Wang, X.; Ye, A.; Zou, Z.; Li, L.; Ye, J.; Zhou, L. Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: A systematic review and meta- analysis. Stem Cell Res. Ther., 2023, 14(1), 301. doi: 10.1186/s13287-023-03518-x PMID: 37864199
  52. Pang, Q.M.; Deng, K.Q.; Zhang, M.; Wu, X.C.; Yang, R.L.; Fu, S.P.; Lin, F.Q.; Zhang, Q.; Ao, J.; Zhang, T. Multiple strategies enhance the efficacy of MSCs transplantation for spinal cord injury. Biomed. Pharmacother., 2023, 157, 114011. doi: 10.1016/j.biopha.2022.114011 PMID: 36410123
  53. García-Bernal, D.; García-Arranz, M.; Yáñez, R.M.; Hervás-Salcedo, R.; Cortés, A.; Fernández-García, M.; Hernando-Rodríguez, M.; Quintana-Bustamante, Ó.; Bueren, J.A.; García-Olmo, D.; Moraleda, J.M.; Sego via, J.C.; Zapata, A.G. The current status of mesenchymal stromal cells: Controversies, unresolved issues and some promising solutions to improve their therapeutic efficacy. Front. Cell Dev. Biol., 2021, 9, 650664. doi: 10.3389/fcell.2021.650664 PMID: 33796536
  54. Yuan, M.; Hu, X.; Yao, L.; Jiang, Y.; Li, L. Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease. Stem Cell Res. Ther., 2022, 13(1), 179. doi: 10.1186/s13287-022-02858-4 PMID: 35505419
  55. Fathy, M.; Okabe, M.; Saad Eldien, H.M.; Yoshida, T. AT-MSCs antifibrotic activity is improved by eugenol through modulation of tgf-β/smad signaling pathway in rats. Molecules, 2020, 25(2), 348. doi: 10.3390/molecules25020348 PMID: 31952158
  56. Jang, Y.O.; Kim, S.H.; Cho, M.Y.; Kim, K.S.; Park, K.S.; Cha, S.K.; Kim, M.Y.; Chang, S.J.; Baik, S.K. Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis. Biochem. Biophys. Res. Commun., 2018, 497(1), 264-271. doi: 10.1016/j.bbrc.2018.02.067 PMID: 29428718
  57. Iwasawa, T.; Nojiri, S.; Tsuchiya, A.; Takeuchi, S.; Watanabe, T.; Ogawa, M.; Motegi, S.; Sato, T.; Kumagai, M.; Nakaya, T.; Ohbuchi, K.; Nahata, M.; Fujitsuka, N.; Takamura, M.; Terai, S. Combination therapy of Juzentaihoto and mesenchymal stem cells attenuates liver damage and regresses fibrosis in mice. Regen. Ther., 2021, 18, 231-241. doi: 10.1016/j.reth.2021.07.002 PMID: 34409135
  58. Mazhari, S.; Gitiara, A.; Baghaei, K.; Hatami, B.; Rad, R.E.; Asadirad, A.; Joharchi, K.; Tokhanbigli, S.; Hashemi, S.M.; Łos, M.J.; Aghdaei, H.A.; Zali, M.R.; Ghavami, S. Therapeutic potential of bone marrow-derived mesenchymal stem cells and imatinib in a rat model of liver fibrosis. Eur. J. Pharmacol., 2020, 882, 173263. doi: 10.1016/j.ejphar.2020.173263 PMID: 32535098
  59. Rafiq, H.; Ayaz, M.; Khan, H.A.; Iqbal, M.; Quraish, S.; Afridi, S.G.; Khan, A.; Khan, B.; Sher, A.; Siraj, F.; Shams, S. Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model. Braz. J. Biol., 2024, 84, e253061. doi: 10.1590/1519-6984.253061 PMID: 35293541
  60. Baghaei, K.; Mazhari, S.; Tokhanbigli, S.; Parsamanesh, G.; Alavifard, H.; Schaafsma, D.; Ghavami, S. Therapeutic potential of targeting regulatory mechanisms of hepatic stellate cell activation in liver fibrosis. Drug Discov. Today, 2022, 27(4), 1044-1061. doi: 10.1016/j.drudis.2021.12.012 PMID: 34952225
  61. Higashi, T.; Friedman, S.L.; Hoshida, Y. Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev., 2017, 121, 27-42. doi: 10.1016/j.addr.2017.05.007 PMID: 28506744
  62. Guo, P.C.; Zuo, J.; Huang, K.K.; Lai, G.Y.; Zhang, X.; An, J.; Li, J.X.; Li, L.; Wu, L.; Lin, Y.T.; Wang, D.Y.; Xu, J.S.; Hao, S.J.; Wang, Y.; Li, R.H.; Ma, W.; Song, Y.M.; Liu, C.; Liu, C.Y.; Dai, Z.; Xu, Y.; Sharma, A.D.; Ott, M.; Ou-Yang, Q.; Huo, F.; Fan, R.; Li, Y.Y.; Hou, J.L.; Volpe, G.; Liu, L.Q.; Esteban, M.A.; Lai, Y.W. Cell atlas of CCl 4-induced progressive liver fibrosis reveals stage-specific responses. Zool. Res., 2023, 44(3), 451-466. doi: 10.24272/j.issn.2095-8137.2023.031 PMID: 36994536
  63. Gandhi, C.R. Hepatic stellate cell activation and pro-fibrogenic signals. J. Hepatol., 2017, 67(5), 1104-1105. doi: 10.1016/j.jhep.2017.06.001 PMID: 28939135
  64. Gupta, G; Khadem, F; Uzonna, JE Role of hepatic stellate cell (HSC)-derived cytokines in hepatic inflammation and immunity. Cytokine, 2019, 124, 1. doi: 10.1016/j.cyto.2018.09.004
  65. Martinez-Castillo, M.; Hernandez-Barragan, A.; Flores-Vasconcelos, I.; Galicia-Moreno, M.; Rosique-Oramas, D.; Perez-Hernandez, J.L.; Higuera-De la Tijera, F.; Montalvo-Jave, E.E.; Torre-Delgadillo, A.; Cordero-Perez, P.; Muñoz-Espinosa, L.; Kershenobich, D.; Gutierrez-Reyes, G. Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients. World J. Hepatol., 2021, 13(2), 218-232. doi: 10.4254/wjh.v13.i2.218 PMID: 33708351
  66. Geervliet, E.; Bansal, R. Matrix metalloproteinases as potential biomarkers and therapeutic targets in liver diseases. Cells, 2020, 9(5), 1212. doi: 10.3390/cells9051212 PMID: 32414178
  67. Shan, L.; Wang, F.; Zhai, D.; Meng, X.; Liu, J.; Lv, X. Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis. Biomed. Pharmacother., 2023, 161, 114472. doi: 10.1016/j.biopha.2023.114472 PMID: 37002573
  68. Pistelli, L.; Sansone, C.; Smerilli, A.; Festa, M.; Noonan, D.M.; Albini, A.; Brunet, C. Mmp-9 and il-1β as targets for diatoxanthin and related microalgal pigments: Potential chemopreventive and photoprotective agents. Mar. Drugs, 2021, 19(7), 354. doi: 10.3390/md19070354 PMID: 34206447
  69. Luo, X.Y.; Meng, X.J.; Cao, D.C.; Wang, W.; Zhou, K.; Li, L.; Guo, M.; Wang, P. Transplantation of bone marrow mesenchymal stromal cells attenuates liver fibrosis in mice by regulating macrophage subtypes. Stem Cell Res. Ther., 2019, 10(1), 16. doi: 10.1186/s13287-018-1122-8 PMID: 30635047
  70. Li, Y.; Fan, W.; Link, F.; Wang, S.; Dooley, S. Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease. JHEP Reports, 2022, 4(2), 100397. doi: 10.1016/j.jhepr.2021.100397 PMID: 35059619
  71. Kisseleva, T.; Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol., 2021, 18(3), 151-166. doi: 10.1038/s41575-020-00372-7 PMID: 33128017
  72. Wang, P.; Cui, Y.; Wang, J.; Liu, D.; Tian, Y.; Liu, K.; Wang, X.; Liu, L.; He, Y.; Pei, Y.; Li, L.; Sun, L.; Zhu, Z.; Chang, D.; Jia, J.; You, H. Mesenchymal stem cells protect against acetaminophen hepatotoxicity by secreting regenerative cytokine hepatocyte growth factor. Stem Cell Res. Ther., 2022, 13(1), 94. doi: 10.1186/s13287-022-02754-x PMID: 35246254
  73. Zhao, Y.; Ye, W.; Wang, Y.D.; Chen, W.D. HGF/c-Met: A key promoter in liver regeneration. Front. Pharmacol., 2022, 13, 808855. doi: 10.3389/fphar.2022.808855 PMID: 35370682
  74. Wang, Z.; Du, K.; Jin, N.; Tang, B.; Zhang, W. Macrophage in liver Fibrosis: Identities and mechanisms. Int. Immunopharmacol., 2023, 120, 110357. doi: 10.1016/j.intimp.2023.110357 PMID: 37224653
  75. Song, Y.; Zhang, T.J.; Li, Y.; Gao, Y. Mesenchymal stem cells decrease M1/M2 ratio and alleviate inflammation to improve limb ischemia in mice. Med. Sci. Monit., 2020, 26, e923287. doi: 10.12659/MSM.923287 PMID: 32860388

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