Volume 27, Issue 4 (7-2023)                   IBJ 2023, 27(4): 199-204 | Back to browse issues page


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Rashidi M, Matour E, Beheshtinasab H, Cheraghzadeh M, Shakerian E. Isorhamnetin Exerts Antifibrotic Effects by Attenuating Platelet-Derived Growth Factor-BB-induced HSC-T6 Cells Activation via Suppressing PI3K-AKT Signaling Pathway. IBJ 2023; 27 (4) :199-204
URL: http://ibj.pasteur.ac.ir/article-1-3948-en.html
1- Cellular and Molecular Research Center, Medical Basic Science Research Institute, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, Cellular and Molecular Research Center, Medical Basic Science Research Institute, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2- Cellular and Molecular Research Center, Medical Basic Science Research Institute, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran , e.shakerian@yahoo.com
Abstract:  
Background: Currently, liver fibrosis is growing worldwide; unfortunately, there is no definite cure for this disease.  Hence, understanding the molecular pathways involved in the development of liver fibrosis can help to find a proper treatment. In this study, we aimed to evaluate the effects of isorhamnetin as an antifibrotic agent on platelet-derived growth factor (PDGF)-BB-activated hepatic stellate cells (HSC)-T6 cells in a concentration-dependent manner. We have also attempted to assess signaling pathways that may affect liver fibrosis.
Methods: PDGF-BB was used to activate the HSC-T6 rat hepatic stellate cell line. The activated cells were treated with Isorhamnetin for 24 h. Finally, we compared the mRNA expression level of COLA1 α-SMA and also the level of phosphorylated AKT protein with the control group.
Results: The obtained data revealed a significant increase in the expression level of the COLA1 and α-SMA genes (p > 0.05), as well as phosphorylated AKT protein, in the cells treated with PDGF-BB. In addition, 75 and 100 µM concentrations of Isorhamnetin markedly declined the COLA1 and α-SMA expression and also the phosphorylated AKT protein level in the HSC-T6 cells.
Conclusions: Our findings suggest that Isorhamnetin decreases HSC-T6 activation, the expression of COLA1 and α-SMA, in vitro, which could act as an antifibrotic element to reduce and treat liver fibrosis disease.
Type of Study: Brief Report | Subject: Cancer Biology
* Corresponding Author Address: Cellular and Molecular Research Center, Medical Basic Science Research Institute, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

References
1. Liu X, Xu J. Calling a stage-based treatment model for chronic liver diseases in China mainland. Annals of hepatology 2020; 19(6): 585-589. [DOI:10.1016/j.aohep.2019.09.007]
2. Davison S. Assessment of liver disease in cystic fibrosis. Paediatric respiratory reviews 2018; 27: 24-27. [DOI:10.1016/j.prrv.2018.05.010]
3. Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008; 134(6): 1655-1669. [DOI:10.1053/j.gastro.2008.03.003]
4. Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best practice and research clinical gastroenterology 2011; 25(2): 195-206. [DOI:10.1016/j.bpg.2011.02.005]
5. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nature reviews Gastroenterology and hepatology 2017; 14(7): 397-411. [DOI:10.1038/nrgastro.2017.38]
6. Afarin R, Rezaeibabaahmadi H, Yaghouti SH, Mohammad taghvaei N. The effect of cholesterol on the activation of TGF-β/Smad3C signaling pathway in hepatic stellate cells and its role in the progression of liver fibrogenesis. Journal of isfahan medical school 2021; 39(619): 212-218.
7. Kweon Y-O, Paik YH, Schnabl B, Qian T, Lemasters JJ, Brenner DA. Gliotoxin-mediated apoptosis of activated human hepatic stellate cells. Journal of hepatology 2003; 39(1): 38-46. [DOI:10.1016/S0168-8278(03)00178-8]
8. Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiological reviews 2008; 88(1): 125-172. [DOI:10.1152/physrev.00013.2007]
9. Baues M, Dasgupta A, Ehling J, Prakash J, Boor P, Tacke F, Kiessling F, Lammers T. Fibrosis imaging: Current concepts and future directions. Advanced drug delivery reviews 2017; 121: 9-26. [DOI:10.1016/j.addr.2017.10.013]
10. Pinzani M, Milani S, Herbst H, DeFranco R, Grappone C, Gentilini A, Caligiuri A, Pellegrini G, Ngo DV, Romanelli RG, Gentilini P. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. The american journal of pathology 1996; 148(3): 785-800.
11. Sancho-Bru P, Juez E, Moreno M, Khurdayan V, Morales-Ruiz M, Colmenero J, Arroyo V, Brenner DA, Ginès P, Bataller R. Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells. Liver International 2010; 30(1): 31-41. [DOI:10.1111/j.1478-3231.2009.02161.x]
12. Reif S, Lang A, Lindquist JN, Yata Y, Gäbele E, Scanga A, Brenner DA, Rippe RA. The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression. Journal of biological chemistry 2003; 278(10): 8083-8090. [DOI:10.1074/jbc.M212927200]
13. Mohamed Abdelgawad L, Abdullatif Abdelaziz A, Bawady El-Begawey M, Mohamed Saafan A. Influence of nanocurcumin and photodynamic therapy using nanocurcumin in treatment of rat tongue oral squamous cell carcinoma through histological examination and gene expression of BCL2 and Caspase-3. Reports of biochemistry and molecular biology 2023; 11(4): 730-738. [DOI:10.52547/rbmb.11.4.730]
14. Lu X, Liu T, Chen K, Xia Y, Dai W, Xu S, Xu L, Wang F, Wu L, Li J, Li S, Wang W, Yu Q, Feng J, Fan X, Zhou Y, Niu P, Guo C. Isorhamnetin: A hepatoprotective flavonoid inhibits apoptosis and autophagy via P38/PPAR-α pathway in mice. Biomedicine and pharmacotherapy 2018; 103: 800-811. [DOI:10.1016/j.biopha.2018.04.016]
15. Nan Y, Su HC, Lian XM, Wu J, Liu S, Chen PP, Liu SM. Pathogenesis of liver fibrosis and its TCM therapeutic perspectives. Evidence-based complementary and alternative medicine 2022; 2022: 5325431. [DOI:10.1155/2022/5325431]
16. Yang JH, Kim SC, Kim KM, Jang CH, Cho SS, Kim SJ, Ku SK, Cho IJ, Ki SH. Isorhamnetin attenuates liver fibrosis by inhibiting TGF-β/Smad signaling and relieving oxidative stress. European journal of pharmacology 2016; 783: 92-102. [DOI:10.1016/j.ejphar.2016.04.042]
17. Vogel S, Piantedosi R, Frank J, Lalazar A, Rockey DC, Friedman SL, Blaner WS. An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro. Journal of lipid research 2000; 41(6): 882-893. [DOI:10.1016/S0022-2275(20)32030-7]
18. Miao CG, Yang YY, He X, Huang C, Huang Y, Zhang L, Lv XW, Jin Y, Li J. Wnt signaling in liver fibrosis: progress, challenges and potential directions. Biochimie 2013; 95(12): 2326-2335. [DOI:10.1016/j.biochi.2013.09.003]
19. Li X, Jin Q, Wu YL, Sun P, Jiang S, Zhang Y, Zhang DQ, Zhang YJ, Lian LH, Nan JX. Tetrandrine regulates hepatic stellate cell activation via TAK1 and NF-κB signaling. International immunopharmacology 2016; 36: 263-270. [DOI:10.1016/j.intimp.2016.04.039]
20. Choi HJ, Soh YJ. An assay method for screening inhibitors of prolyl 4-hydroxylase in immortalized rat hepatic stellate HSC-T6 cells. Biomolecules and therapeutics 2007; 15(4): 261-265. [DOI:10.4062/biomolther.2007.15.4.261]
21. Wang Y, Yan D. Plantamajoside exerts antifibrosis effects in the liver by inhibiting hepatic stellate cell activation. Experimental and therapeutic medicine 2019; 18(4): 2421-2428. [DOI:10.3892/etm.2019.7843]
22. Yang L, Zhang CZ, Zhu QJ. Kangxian ruangan keli inhibits hepatic stellate cell proliferation mediated by PDGF. World journal of gastroenterology 2003; 9(9): 2050-2053. [DOI:10.3748/wjg.v9.i9.2050]
23. Herrmann J, Gressner AM, Weiskirchen R. Immortal hepatic stellate cell lines: useful tools to study hepatic stellate cell biology and function? Journal of cellular and molecular medicine 2007; 11(4): 704-722. [DOI:10.1111/j.1582-4934.2007.00060.x]
24. Seki E, Brenner DA. Recent advancement of molecular mechanisms of liver fibrosis. Journal of hepatobiliary pancreatic sciences 2015; 22(7): 512-518. [DOI:10.1002/jhbp.245]
25. Wang C, Li Y, Hi H, Zhang Y, Ying Z, Wang X, Zhang T, Zhang W, Fan Z, Li X, Ma J, Pan X. Disruption of FGF signaling ameliorates inflammatory response in hepatic stellate cells. Frontiers in cell and developmental biology 2020; 8: 601. [DOI:10.3389/fcell.2020.00601]
26. Claveria-Cabello A, Colyn L, Arechederra M, Urman JM, Berasain C, Avila MA, Fernandez-Barrena M. Epigenetics in liver fibrosis: could HDACs be a therapeutic target? Cells 2020; 9(10): 2321. [DOI:10.3390/cells9102321]
27. Wang X, Gao Y, Li Y, Huang Y, Zhu Y, Lv W, Wang R, Gou L, Cheng C, Feng Z, Xie J, Tian J, Yao R. Roseotoxin B alleviates cholestatic liver fibrosis through inhibiting PDGF-B/PDGFR-β pathway in hepatic stellate cells. Cell death and disease 2020; 11(6): 458. [DOI:10.1038/s41419-020-2575-0]
28. Shang X, Yuan H, Dai L, Liu Y, He J, Chen H, Li H, Li X. Anti-liver fibrosis activity and the potential mode of action of Ruangan Granules: Integrated network pharmacology and metabolomics. Frontiers in pharmacology 2021; 12: 754807. [DOI:10.3389/fphar.2021.754807]
29. Liu N, Feng J, Lu X, Yao Z, Liu Q, Lv Y, Han Y, Deng J, Zhou Y. Isorhamnetin inhibits liver fibrosis by reducing autophagy and inhibiting extracellular matrix formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK pathways. Mediators of inflammation 2019; 2019: 6175091. [DOI:10.1155/2019/6175091]
30. Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND, Zhao YY. New insights into TGF-β/Smad signaling in tissue fibrosis. Chemicobiological interactions 2018; 292: 76-83. [DOI:10.1016/j.cbi.2018.07.008]

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