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Human Cell

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Sulforaphane inhibits the activation of hepatic stellate cell by miRNA-423-5p targeting suppressor of fused

  • Ming-Hui Feng
  • Jian-Wei Li
  • Hai-Tao Sun
  • Song-Qi He
  • Jie PangEmail author
Research Article
  • 33 Downloads

Abstract

Liver fibrosis, a common pathological process in chronic liver diseases, is characterized by excessive accumulation of extracellular matrix proteins and considered as a wound healing response to chronic liver injury. Hepatic stellate cell (HSC) activation plays a key role in liver fibrosis development. Previous studies showed that sulforaphane (SFN) has wide protective effects against tissue injury and inflammation. Accumulating evidence has shown that microRNAs play important roles in the development of hepatic fibrosis, some of which have been identified as potential therapeutic targets. This study was conducted to explore the role of SFN in the suppression of HSC activation. Quantitative real-time PCR showed that HSC miR-423-5p levels were up-regulated during HSC activation and down-regulated after SFN administration. Further, transfection of a miR-423-5p mimic demonstrated that inhibition of HSC activation by SFN required down-regulation of miR-423-5p. We showed that suppressor of fused is the direct target of miR-423-5p. SFN may play a role in inhibiting hepatic fibrosis by downregulating miRNA-423-5p. MiRNA-423-5p may be useful as a therapeutic target for treating hepatic fibrosis.

Keywords

Sulforaphane Hepatic stellate cell MicroRNA Suppressor of fused 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation of China [Grant number 81704016] and Natural Science Foundation of Guangdong Province [Grant number 2017A030313687].

Author contributions

P.J. designed the research. F.M-H and L.J-W performed experiments, analyzed the data, and wrote the paper. H.S-Q and S.H-T performed the illustrations of the data. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

References

  1. 1.
    Jiao J, Friedman SL, Aloman C. Hepatic fibrosis. Curr Opin Gastroenterol. 2009;25:223–9.CrossRefGoogle Scholar
  2. 2.
    Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 2001;21:311–36.CrossRefGoogle Scholar
  3. 3.
    Galli A, Crabb DW, Ceni E, et al. Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology. 2002;122:1924–40.CrossRefGoogle Scholar
  4. 4.
    Riccalton-Banks L, Bhandari R, Fry J, Shakesheff KM. A simple method for the simultaneous isolation of stellate cells and hepatocytes from rat liver tissue. Mol Cell Biochem. 2003;248:97–102.CrossRefGoogle Scholar
  5. 5.
    Carpino G, Morini S, Ginanni CS, et al. Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation. Dig Liver Dis. 2005;37:349–56.CrossRefGoogle Scholar
  6. 6.
    Lu DH, Guo XY, Qin SY, et al. Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines. World J Gastroenterol. 2015;21:1531–45.CrossRefGoogle Scholar
  7. 7.
    Tan Z, Qian X, Jiang R, et al. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J Immunol. 2013;191:1835–44.CrossRefGoogle Scholar
  8. 8.
    Baroni GS, D’Ambrosio L, Curto P, et al. Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology. 2010;23:1189–99.CrossRefGoogle Scholar
  9. 9.
    Baroni GS, Pastorelli A, Manzin A, et al. Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C. Liver Int. 2010;19:212–9.CrossRefGoogle Scholar
  10. 10.
    Tsukamoto H. Cytokine regulation of hepatic stellate cells in liver fibrosis. Alcohol Clin Exp Res. 2010;23:911–6.CrossRefGoogle Scholar
  11. 11.
    Li JT, Liao ZX, Ping J, Xu D, Wang H. Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies. J Gastroenterol. 2008;43:419–28.CrossRefGoogle Scholar
  12. 12.
    Schnabl B, Kweon YO, Frederick JP, Wang XF, Rippe RA, Brenner DA. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology. 2001;34:89–100.CrossRefGoogle Scholar
  13. 13.
    Klinkhammer BM, Floege J, Boor P. PDGF in organ fibrosis. Mol Aspects Med. 2018;62:44–62.CrossRefGoogle Scholar
  14. 14.
    Gamet-Payrastre L, Li P, Lumeau S, et al. Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 2000;60:1426–33.Google Scholar
  15. 15.
    Jeon YK, Yoo DR, Jang YH, Jang SJ, Nam MJ. Sulforaphane induces apoptosis in human hepatic cancer cells through inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4, mediated by hypoxia inducible factor-1-dependent pathway. Biochem Biophys Acta. 2011;1814:1340–8.Google Scholar
  16. 16.
    Sayed RH, Khalil WK, Salem HA, Kenawy SA, Elsayeh BM. Sulforaphane increases the survival rate in rats with fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide. Nutr Res. 2014;34:982–9.CrossRefGoogle Scholar
  17. 17.
    Tubbs E, Axelsson AS, Vial G, Wollheim CB, Reuisset J, Rosengren AH. Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production. Mol Cell Endocrinol. 2018;461:S0303720717305014.CrossRefGoogle Scholar
  18. 18.
    Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007;27:91–105.CrossRefGoogle Scholar
  19. 19.
    Doench JG, Sharp PA. Specificity of microRNA target selection in translational repression. Genes Dev. 2004;18:504–11.CrossRefGoogle Scholar
  20. 20.
    Xin X, Zhang Y, Liu X, Xin H, Cao Y, Geng M. MicroRNA in hepatic fibrosis and cirrhosis. Front Biosci. 2014;19:1418–24.CrossRefGoogle Scholar
  21. 21.
    Oh CJ, Kim JY, Min AK, et al. Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-beta/Smad signaling. Free Radic Biol Med. 2012;52:671–82.CrossRefGoogle Scholar
  22. 22.
    Xu L, Hui AY, Albanis E, et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut. 2005;54:142–51.CrossRefGoogle Scholar
  23. 23.
    Losso JN, Truax RE. Comparative inhibitory activities of sulforaphane and phenethyl isothiocyanate against leukemia resistant CEM/C2 cancer cells. J Funct Foods. 2009;1:229–35.CrossRefGoogle Scholar
  24. 24.
    Lu R, Zhao G, Yang Y, et al. Long noncoding RNA HOTAIRM1 inhibits cell progression by regulating miR-17-5p/PTEN axis in gastric cancer. J Cell Biochem. 2019;120:4952–65.CrossRefGoogle Scholar
  25. 25.
    Yang JJ, Tao H, Li J. Hedgehog signaling pathway as key player in liver fibrosis: new insights and perspectives. Expert Opin Ther Targets. 2014;18:1–11.CrossRefGoogle Scholar
  26. 26.
    Huang D, Wang Y, Tang J, Luo S. Molecular mechanisms of suppressor of fused in regulating the hedgehog signalling pathway. Oncol Lett. 2018;15:6077–86.Google Scholar
  27. 27.
    Yang C, Zeisberg M, Mosterman B, et al. Liver fibrosis: insights into migration of hepatic stellate cells in response to extracellular matrix and growth factors. Gastroenterology. 2003;124:147–59.CrossRefGoogle Scholar
  28. 28.
    Lopez ON, Bohanon FJ, Wang X, et al. STAT3 inhibition suppresses hepatic stellate cell fibrogenesis: HJC0123, a potential therapeutic agent for liver fibrosis. Rsc Adv. 2016;6:100652.CrossRefGoogle Scholar
  29. 29.
    Robert S, Gicquel T, Bodin A, Lagente V, Boichot E. Characterization of the MMP/TIMP imbalance and collagen production induced by IL-1β or TNF-α release from human hepatic stellate cells. PLoS One. 2016;11:e0153118.CrossRefGoogle Scholar
  30. 30.
    Moreno-Alvarez P, Sosa-Garrocho M, Briones-Orta MA, et al. Angiotensin II increases mRNA levels of all TGF-β isoforms in quiescent and activated rat hepatic stellate cells. Cell Biol Int. 2013;34:969–78.CrossRefGoogle Scholar
  31. 31.
    Wang J, Chu ES, Lan HY, Sung JJ, Yu J. 207 MicroRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis in vitro and in mice. Gastroenterology. 2013;144:S938.CrossRefGoogle Scholar
  32. 32.
    Okada H, Honda M, Campbell JS, et al. Inhibition of microRNA-214 ameliorates hepatic fibrosis and tumor incidence in platelet-derived growth factor C transgenic mice. Cancer Sci. 2015;106:1143–52.CrossRefGoogle Scholar
  33. 33.
    Martin SL, Kala R, Ollefsbol TO. Mechanisms for inhibition of colon cancer cells by sulforaphane through epigenetic modulation of microRNA-21 and human telomerase reverse transcriptase (hTERT) down-regulation. Curr Cancer Drug Targets. 2017;18:97–106.CrossRefGoogle Scholar
  34. 34.
    Perrot CY, Javelaud D, Mauviel A. Overlapping activities of TGF-beta and Hedgehog signaling in cancer: therapeutic targets for cancer treatment. Pharmacol Ther. 2013;137:183–99.CrossRefGoogle Scholar
  35. 35.
    Sicklick JK, Li YX, Choi SS, et al. Role for Hedgehog signaling in hepatic stellate cell activation and viability. Lab Invest. 2005;85:1368–80.CrossRefGoogle Scholar
  36. 36.
    Lee JH, Jang EJ, Seo HL, et al. Sauchinone attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway. Chem Biol Interact. 2014;224:58–67.CrossRefGoogle Scholar

Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Ming-Hui Feng
    • 1
  • Jian-Wei Li
    • 2
  • Hai-Tao Sun
    • 2
  • Song-Qi He
    • 2
  • Jie Pang
    • 2
    Email author
  1. 1.The Third Affiliated Hospital Of Guangzhou University of Chinese MedicineGuangzhouChina
  2. 2.School of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouChina

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