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2018 | 23 |

Tytuł artykułu

Loureirin B inhibits the proliferation of hepatic stellate cells and the Wnt/β-catenin signaling pathway by regulating miR-148-3p

Autorzy

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Background: We investigated the activity of loureirin B against liver fibrosis and the underlying molecular mechanisms. Methods: Hepatic stellate cells (HSCs) from Sprague-Dawley rats were treated with different concentrations of loureirin B. We used the MTT assay to determine HSC proliferation, flow cytometry to analyze apoptosis, and western blot to determine the expressions of Bax, Bcl-2, Wnt1 and β-catenin. Real-time PCR was used to determine the expressions of Wnt1 and miR-148-3p. Results: The MTT assay showed that loureirin B treatment significantly inhibited the proliferation of HSCs in time- and dose-dependent manners. Loureirin B significantly promoted the apoptosis of HSCs, increased the expression of Bax and decreased the Bcl-2 level. Western blot analysis showed that the expressions of Wnt1 and β-catenin were obviously lower in the loureirin B treatment group than in the control group. We also found that loureirin B could decrease the Wnt1 mRNA level and increase miR-148-3p expression. Knockdown of miR-148-3p using inhibitor could reverse the effects of loureirin B on the proliferation and apoptosis of HSCs and the expressions of Bax, Bcl-2, Wnt1 and β-catenin. Conclusion: Our results suggest that loureirin B inhibited the proliferation and promoted the apoptosis of HSCs, and suppressed the Wnt/β-catenin signaling pathway via regulation of miR-148-3p.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

23

Opis fizyczny

p.1-10,fig.,ref.

Twórcy

autor
  • Department of Gastroenterology, the First People’s Hospital of Yunnan province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan province, China
autor
  • Department of Gastroenterology, the First People’s Hospital of Yunnan province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan province, China
autor
  • Department of Gastroenterology, the First People’s Hospital of Yunnan province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan province, China
autor
  • Department of Gastroenterology, the First People’s Hospital of Yunnan province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan province, China

Bibliografia

  • 1. Lan T, Li C, Yang G, Sun Y, Zhuang L, Ou Y, Li H, Wang G, Kisseleva T, Brenner D, Guo J. Sphingosine kinase 1 promotes liver fibrosis by preventing miR-19b-3p-mediated inhibition of CCR2. Hepatology. 2018; https://doi.org/ 10.1002/hep.29885.
  • 2. Yang MD, Chiang YM, Higashiyama R, Asahina K, Mann DA, Mann J, Wang CC, Tsukamoto H. Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator-activated receptor gamma in hepatic stellate cells for their antifibrotic effect. Hepatology. 2012;55:1271–81. https://doi.org/10.1002/hep.24792.
  • 3. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol. 2011;6:425–56. https://doi.org/10. 1146/annurev-pathol-011110-130246.
  • 4. Shi MN, Huang YH, Zheng WD, Zhang LJ, Chen ZX, Wang XZ. Relationship between transforming growth factor beta1 and anti-fibrotic effect of interleukin-10. World J Gastroenterol. 2006;12:2357–62.
  • 5. Qin S, Jiang H, Su S, Wang D, Liang Z, Zhang J, Yang W. Inhibition of hepatic stellate cell proliferation by bone marrow mesenchymal stem cells via regulation of the cell cycle in rat. Exp Ther Med. 2012;4:375–80. https://doi. org/10.3892/etm.2012.628.
  • 6. He T, Bai X, Yang L, Fan L, Li Y, Su L, Gao J, Han S, Hu D. Loureirin B Inhibits Hypertrophic Scar Formation via Inhibition of the TGF-beta1-ERK/JNK Pathway. Cell Physiol Biochem. 2015;37:666–76. https://doi.org/10.1159/ 000430385.
  • 7. Bai X, He T, Liu J, Wang Y, Fan L, Tao K, Shi J, Tang C, Su L, Hu D. Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-beta/Smad pathway. Exp Dermatol. 2015;24:355–60. https://doi.org/10.1111/exd.12665.
  • 8. Xiang T, Zhang S, Cheng N, Ge S, Wen J, Xiao J, Wu X. Oxidored-nitro domain-containing protein 1 promotes liver fibrosis by activating the Wnt/beta-catenin signaling pathway in vitro. Mol Med Rep. 2017;16:5050–4. https://doi. org/10.3892/mmr.2017.7165.
  • 9. Zheng J, Wang W, Yu F, Dong P, Chen B, Zhou MT. MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting Epithelial-to-Mesenchymal Transition. Cell Physiol Biochem. 2018;46:82–92. https://doi.org/10. 1159/000488411.
  • 10. Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 2001;21:311–35. https://doi.org/10.1055/s-2001-17550.
  • 11. Friedman SL. Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med. 1993;328:1828–35. https://doi.org/10.1056/ NEJM199306243282508.
  • 12. Casu A, Canepa M, Nanni G. Perisinusoidal stellate cells or Ito cells and their role in hepatic fibrosis. Pathologica. 1994;86:467–99.
  • 13. Senoo H, Sato M, Imai K. Hepatic stellate cells–from the viewpoint of retinoid handling and function of the extracellular matrix. Kaibogaku Zasshi. 1997;72:79–94.
  • 14. Hendriks HF, Verhoofstad WA, Brouwer A, de Leeuw AM, Knook DL. Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver. Exp Cell Res. 1985;160:138–49.
  • 15. Wake K. Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol. 1980;66:303–53.
  • 16. Senoo H, Imai K, Matano Y, Sato M. Molecular mechanisms in the reversible regulation of morphology, proliferation and collagen metabolism in hepatic stellate cells by the three-dimensional structure of the extracellular matrix. J Gastroenterol Hepatol. 1998;13:S19–32. https://doi.org/10.1111/jgh.1998.13.s1.19.
  • 17. Sha Y, Zhang Y, Cao J, Qian K, Niu B, Chen Q. Loureirin B promotes insulin secretion through inhibition of KATP channel and influx of intracellular calcium. J Cell Biochem. 2018;119:2012–21. https://doi.org/10.1002/jcb.26362.
  • 18. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210. https://doi.org/10.1002/path.2277.
  • 19. Mabuchi A, Mullaney I, Sheard PW, Hessian PA, Mallard BL, Tawadrous MN, Zimmermann A, Senoo H, Wheatley AM. Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat. J Hepatol. 2004;40:910–6. https://doi.org/10.1016/j.jhep.2004.02.005.
  • 20. Jiang Y, Zhang G, Yan D, Yang H, Ye Z, Ma T. Bioactivity-Guided Fractionation of the Traditional Chinese Medicine Resina Draconis Reveals Loureirin B as a PAI-1 Inhibitor. Evid Based Complement Alternat Med. 2017;2017:9425963. https://doi.org/10.1155/2017/9425963.
  • 21. Sun H, Chen G, Wen B, Sun J, An H, Pang J, Xu W, Yang X, He S. Oligo-peptide I-C-F-6 inhibits hepatic stellate cell activation and ameliorates CCl4-induced liver fibrosis by suppressing NF-kappaB signaling and Wnt/beta-catenin signaling. J Pharmacol Sci. 2018; https://doi.org/10.1016/j.jphs.2018.01.003.
  • 22. Daniels DL, Eklof Spink K, Weis WI. beta-catenin: molecular plasticity and drug design. Trends Biochem Sci. 2001; 26:672–8.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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