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Article Open Access

Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro

  • Authors:
    • Yinhe Tang
    • Qiyu Zhang
    • Yefan Zhu
    • Gang Chen
    • Fuxiang Yu
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
    Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1647-1653
    |
    Published online on: February 14, 2017
       https://doi.org/10.3892/mmr.2017.6201
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Abstract

Hepatic stellate cell (HSC) activation serves a key role in liver fibrosis, and is associated with chronic liver diseases. Bilirubin, a product of heme degradation, has been demonstrated to have antioxidant properties. The present study investigated the effects of physiological concentrations of bilirubin on rat HSC activation. Rat HSCs were isolated and cultured for several generations to induce activation. The activated HSCs were subsequently treated with 0, 1, 10 or 20 mg/l bilirubin and assayed for parameters of cell activation. As the bilirubin concentration increased, HSCs demonstrated reduced production of reactive oxygen species, reduced protein expression levels of α‑smooth muscle actin, a decreased mRNA expression ratio of tissue inhibitor of matrix metalloproteinase‑1/matrix metalloproteinase‑2, decreased proliferation and increased apoptosis. In conclusion, elevated bilirubin levels, within its physiological concentration range, appeared to inhibit HSC activation. These findings suggested a potential role for bilirubin in the treatment of fibrosis that requires further investigation.
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1 

Geerts A: History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 21:311–335. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Brandão DF, Ramalho LN, Ramalho FS, Zucoloto S, Martinelli Ade L and Silva Ode C: Liver cirrhosis and hepatic stellate cells. Acta Cir Bras. 21 Suppl 1:S54–S57. 2006. View Article : Google Scholar

3 

Li JT, Liao ZX, Ping J, Xu D and Wang H: Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies. J Gastroenterol. 43:419–428. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Atzori L, Poli G and Perra A: Hepatic stellate cell: A star cell in the liver. Int J Biochem Cell Biol. 41:1639–1642. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Tomaro ML and Batlle AM: Bilirubin: Its role in cytoprotection against oxidative stress. Int J Biochem Cell Biol. 34:216–220. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Washington K, Wright K, Shyr Y, Hunter EB, Olson S and Raiford DS: Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver. Hum Pathol. 31:822–828. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Stocker R, Yamamoto Y, McDonagh AF, Glazer AN and Ames BN: Bilirubin is an antioxidant of possible physiological importance. Science. 235:1043–1046. 1987. View Article : Google Scholar : PubMed/NCBI

8 

Wu TW, Fung KP, Wu J, Yang CC and Weisel RD: Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins. Biochem Pharmacol. 51:859–862. 1996. View Article : Google Scholar : PubMed/NCBI

9 

Yamaguchi T, Horio F, Hashizume T, Tanaka M, Ikeda S, Kakinuma A and Nakajima H: Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo. Biochem Biophys Res Commun. 214:11–19. 1995. View Article : Google Scholar : PubMed/NCBI

10 

Hansen TW: Bilirubin production, breast-feeding and neonatal jaundice. Acta Paediatr. 90:716–717. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Gitto E, Reiter RJ, Karbownik M, Tan DX, Gitto P, Barberi S and Barberi I: Causes of oxidative stress in the pre- and perinatal period. Biol Neonate. 81:146–157. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, Qian T, Schoonhoven R, Hagedorn CH, Lemasters JJ and Brenner DA: NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest. 112:1383–1394. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Zhong Z, Froh M, Wheeler MD, Smutney O, Lehmann TG and Thurman RG: Viral gene delivery of superoxide dismutase attenuates experimental cholestasis-induced liver fibrosis in the rat. Gene Ther. 9:183–191. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Ahmad A and Ahmad R: Resveratrol mitigate structural changes and hepatic stellate cell activation in N'-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage. Chem Biol Interact. 221:1–12. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Yu FX, Teng YY, Zhu QD, Zhang QY and Tang YH: Inhibitory effects of capsaicin on hepatic stellate cells and liver fibrosis. Biochem Cell Biol. 92:406–412. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Yu F, Su L, Ji S, Zhang S, Yu P, Zheng Y and Zhang Q: Inhibition of hepatic stellate cell activation and liver fibrosis by fat-specific protein 27. Mol Cell Biochem. 369:35–43. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Elsharkawy AM, Oakley F and Mann DA: The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. Apoptosis. 10:927–939. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Choi SS, Sicklick JK, Ma Q, Yang L, Huang J, Qi Y, Chen W, Li YX, Goldschmidt-Clermont PJ and Diehl AM: Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice. Hepatology. 44:1267–1277. 2006. View Article : Google Scholar : PubMed/NCBI

19 

McCarty MF, Barroso-Aranda J and Contreras F: Genistein and phycocyanobilin may prevent hepatic fibrosis by suppressing proliferation and activation of hepatic stellate cells. Med Hypotheses. 72:330–332. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Jiang F, Roberts SJ, Datla Sr and Dusting GJ: NO modulates NADPH oxidase function via heme oxygenase-1 in human endothelial cells. Hypertension. 48:950–957. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Kikuchi G, Yoshida T and Noguchi M: Heme oxygenase and heme degradation. Biochem Biophys Res Commun. 338:558–567. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Li L, Grenard P, Nhieu JT, Julien B, Mallat A, Habib A and Lotersztajn S: Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibroblasts. Gastroenterology. 125:460–469. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Tsui TY, Lau CK, Ma J, Glockzin G, Obed A, Schlitt HJ and Fan ST: Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats. World J Gastroenterol. 12:2016–2023. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Lanone S, Bloc S, Foresti R, Almolki A, Taillé C, Callebert J, Conti M, Goven D, Aubier M, Dureuil B, et al: Bilirubin decreases nos2 expression via inhibition of NAD(P)H oxidase: Implications for protection against endotoxic shock in rats. FASEB J. 19:1890–1892. 2005.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tang Y, Zhang Q, Zhu Y, Chen G and Yu F: Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro. Mol Med Rep 15: 1647-1653, 2017.
APA
Tang, Y., Zhang, Q., Zhu, Y., Chen, G., & Yu, F. (2017). Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro. Molecular Medicine Reports, 15, 1647-1653. https://doi.org/10.3892/mmr.2017.6201
MLA
Tang, Y., Zhang, Q., Zhu, Y., Chen, G., Yu, F."Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro". Molecular Medicine Reports 15.4 (2017): 1647-1653.
Chicago
Tang, Y., Zhang, Q., Zhu, Y., Chen, G., Yu, F."Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro". Molecular Medicine Reports 15, no. 4 (2017): 1647-1653. https://doi.org/10.3892/mmr.2017.6201
Copy and paste a formatted citation
x
Spandidos Publications style
Tang Y, Zhang Q, Zhu Y, Chen G and Yu F: Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro. Mol Med Rep 15: 1647-1653, 2017.
APA
Tang, Y., Zhang, Q., Zhu, Y., Chen, G., & Yu, F. (2017). Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro. Molecular Medicine Reports, 15, 1647-1653. https://doi.org/10.3892/mmr.2017.6201
MLA
Tang, Y., Zhang, Q., Zhu, Y., Chen, G., Yu, F."Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro". Molecular Medicine Reports 15.4 (2017): 1647-1653.
Chicago
Tang, Y., Zhang, Q., Zhu, Y., Chen, G., Yu, F."Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro". Molecular Medicine Reports 15, no. 4 (2017): 1647-1653. https://doi.org/10.3892/mmr.2017.6201
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