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International Journal of Molecular Medicine
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Article

Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis

  • Authors:
    • Nanzheng Chen
    • Qianqian Geng
    • Jianbao Zheng
    • Sai He
    • Xiongwei Huo
    • Xuejun Sun
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 1110-1116
    |
    Published online on: July 25, 2014
       https://doi.org/10.3892/ijmm.2014.1867
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Abstract

The hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis have rarely been discussed and its mechanisms of action in alcohol-induced liver disease remain unknown. In this study, serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess hepatic function; histopathological and immunohistochemical observations were used to evaluate pathological and specific molecular changes in liver tissue and flow cytometry was used to detect the apoptosis in cultured hepatic stellate cells (HSCs), the major fibrogenic cells in the liver; PCR and western blot analysis were employed to evaluate the changes in the expression of molecules and signaling pathways. We demonstrate that curcumin alleviates alcohol-induced hepatic fibrosis by affecting the HSCs. We found that the administration of curcumin inhibited alcohol-induced HSC proliferation and even induced HSC apoptosis by stimulating endoplasmic reticulum (ER) stress. We also found that by suppressing the transforming growth factor-β (TGF-β)/Smad signaling pathway, the administration of curcumin impaired the production of extracellular matrix proteins in alcohol-stimulated HSCs. These results indicate that curcumin exerts its hepatoprotective effects against alcohol-induced hepatic fibrosis by inhibiting the proliferation and inducing the apoptosis of HSCs by stimulating ER stress and deactivating HSCs by suppressing the TGF-β/Smad signaling pathway.
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1 

Williams R: Global challenges in liver disease. Hepatology. 44:521–526. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Mandayam S, Jamal MM and Morgan TR: Epidemiology of alcoholic liver disease. Semin Liver Dis. 24:217–232. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Poli G: Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med. 21:49–98. 2000. View Article : Google Scholar

4 

Brenner DA: Molecular pathogenesis of liver fibrosis. Trans Am Clin Climatol Assoc. 120:361–368. 2009.PubMed/NCBI

5 

Senoo H: Structure and function of hepatic stellate cells. Med Electron Microsc. 37:3–15. 2004. View Article : Google Scholar

6 

Gao B and Bataller R: Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 141:1572–1585. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Siegmund SV, Dooley S and Brenner DA: Molecular mechanisms of alcohol-induced hepatic fibrosis. Dig Dis. 23:264–274. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Dooley S, Streckert M, Delvoux B and Gressner AM: Expression of Smads during in vitro transdifferentiation of hepatic stellate cells to myofibroblasts. Biochem Biophys Res Commun. 283:554–562. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Shi Y and Massague J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113:685–700. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Kavsak P, Rasmussen RK, Causing CG, et al: Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 6:1365–1375. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Chen K, Zhang S, Ji Y, et al: Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway. PLoS One. 8:e729272013. View Article : Google Scholar : PubMed/NCBI

13 

Wu L, Cai B, Zheng S, Liu X, Cai H and Li H: Effect of emodin on endoplasmic reticulum stress in rats with severe acute pancreatitis. Inflammation. 36:1020–1029. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Geng J, Peng W, Huang Y, Fan H and Li S: Ginsenoside-Rg1 from Panax notoginseng prevents hepatic fibrosis induced by thioacetamide in rats. Eur J Pharmacol. 634:162–169. 2010. View Article : Google Scholar : PubMed/NCBI

15 

O’Connell MA and Rushworth SA: Curcumin: potential for hepatic fibrosis therapy? Br J Pharmacol. 153:403–405. 2008.

16 

Noorafshan A and Ashkani-Esfahani S: A review of therapeutic effects of curcumin. Curr Pharm Des. 19:2032–2046. 2013.PubMed/NCBI

17 

Tu CT, Yao QY, Xu BL, Wang JY, Zhou CH and Zhang SC: Protective effects of curcumin against hepatic fibrosis induced by carbon tetrachloride: modulation of high-mobility group box 1, Toll-like receptor 4 and 2 expression. Food Chem Toxicol. 50:3343–3351. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Yao QY, Xu BL, Wang JY, Liu HC, Zhang SC and Tu CT: Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats. BMC Complement Altern Med. 12:1562012. View Article : Google Scholar : PubMed/NCBI

19 

Kim JM, Kim HG, Han JM, et al: The herbal formula CGX ameliorates the expression of vascular endothelial growth factor in alcoholic liver fibrosis. J Ethnopharmacol. 150:892–900. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Bruck R, Ashkenazi M, Weiss S, et al: Prevention of liver cirrhosis in rats by curcumin. Liver Int. 27:373–383. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Wang Y, Cheng M, Zhang B, Nie F and Jiang H: Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats. PLoS One. 8:e586592013. View Article : Google Scholar : PubMed/NCBI

22 

Traber PG, Chou H, Zomer E, et al: Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One. 8:e753612013. View Article : Google Scholar : PubMed/NCBI

23 

Su LJ, Chang CC, Yang CH, et al: Graptopetalum paraguayense ameliorates chemical-induced rat hepatic fibrosis in vivo and inactivates stellate cells and Kupffer cells in vitro. PLoS One. 8:e539882013. View Article : Google Scholar : PubMed/NCBI

24 

Liu ZW, Zhu HT, Chen KL, et al: Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy. Cardiovasc Diabetol. 12:1582013. View Article : Google Scholar

25 

Bataller R and Brenner DA: Liver fibrosis. J Clin Invest. 115:209–218. 2005. View Article : Google Scholar

26 

Lee UE and Friedman SL: Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 25:195–206. 2011. View Article : Google Scholar

27 

Padhye S, Chavan D, Pandey S, Deshpande J, Swamy KV and Sarkar FH: Perspectives on chemopreventive and therapeutic potential of curcumin analogs in medicinal chemistry. Mini Rev Med Chem. 10:372–387. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Sharma RA, Gescher AJ and Steward WP: Curcumin: the story so far. Eur J Cancer. 41:1955–1968. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Fu Y, Zheng S, Lin J, Ryerse J and Chen A: Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol. 73:399–409. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Rivera-Espinoza Y and Muriel P: Pharmacological actions of curcumin in liver diseases or damage. Liver Int. 29:1457–1466. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Sun X, He Y, Ma TT, Huang C, Zhang L and Li J: Participation of miR-200a in TGF-β1-mediated hepatic stellate cell activation. Mol Cell Biochem. 388:11–23. 2014.

32 

Kodama T, Takehara T, Hikita H, et al: Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice. J Clin Invest. 121:3343–3356. 2011. View Article : Google Scholar

33 

Friedman SL: Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 7:425–436. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Ron D and Walter P: Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 8:519–529. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Rao RV, Ellerby HM and Bredesen DE: Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11:372–380. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Lee AS: The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods. 35:373–381. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Roberts AB, Tian F, Byfield SD, et al: Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev. 17:19–27. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Leask A and Abraham DJ: TGF-beta signaling and the fibrotic response. FASEB J. 18:816–827. 2004. View Article : Google Scholar : PubMed/NCBI

39 

Bissell DM, Roulot D and George J: Transforming growth factor beta and the liver. Hepatology. 34:859–867. 2001. View Article : Google Scholar : PubMed/NCBI

40 

Schnabl B, Kweon YO, Frederick JP, Wang XF, Rippe RA and Brenner DA: The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology. 34:89–100. 2001. View Article : Google Scholar : PubMed/NCBI

41 

Liu C, Gaca MD, Swenson ES, Vellucci VF, Reiss M and Wells RG: Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-beta-independent. J Biol Chem. 278:11721–11728. 2003. View Article : Google Scholar

42 

Friedman SL: Mechanisms of hepatic fibrogenesis. Gastroenterology. 134:1655–1669. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen N, Geng Q, Zheng J, He S, Huo X and Sun X: Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis. Int J Mol Med 34: 1110-1116, 2014.
APA
Chen, N., Geng, Q., Zheng, J., He, S., Huo, X., & Sun, X. (2014). Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis. International Journal of Molecular Medicine, 34, 1110-1116. https://doi.org/10.3892/ijmm.2014.1867
MLA
Chen, N., Geng, Q., Zheng, J., He, S., Huo, X., Sun, X."Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis". International Journal of Molecular Medicine 34.4 (2014): 1110-1116.
Chicago
Chen, N., Geng, Q., Zheng, J., He, S., Huo, X., Sun, X."Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis". International Journal of Molecular Medicine 34, no. 4 (2014): 1110-1116. https://doi.org/10.3892/ijmm.2014.1867
Copy and paste a formatted citation
x
Spandidos Publications style
Chen N, Geng Q, Zheng J, He S, Huo X and Sun X: Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis. Int J Mol Med 34: 1110-1116, 2014.
APA
Chen, N., Geng, Q., Zheng, J., He, S., Huo, X., & Sun, X. (2014). Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis. International Journal of Molecular Medicine, 34, 1110-1116. https://doi.org/10.3892/ijmm.2014.1867
MLA
Chen, N., Geng, Q., Zheng, J., He, S., Huo, X., Sun, X."Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis". International Journal of Molecular Medicine 34.4 (2014): 1110-1116.
Chicago
Chen, N., Geng, Q., Zheng, J., He, S., Huo, X., Sun, X."Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis". International Journal of Molecular Medicine 34, no. 4 (2014): 1110-1116. https://doi.org/10.3892/ijmm.2014.1867
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