The S protein of hepatitis B virus promotes collagen type I expression in hepatic stellate cells by virtue of hepatocytes

Liu,Xudong; Tu,Yanyun; Deng,Xin; Liang,Jian

doi:10.3892/br.2013.201

The S protein of hepatitis B virus promotes collagen type I expression in hepatic stellate cells by virtue of hepatocytes

Authors:
- Xudong Liu
- Yanyun Tu
- Xin Deng
- Jian Liang
View Affiliations

Affiliations: Department of Liver Diseases, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China
Published online on: November 19, 2013 https://doi.org/10.3892/br.2013.201
Pages: 97-100

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

This study was conducted in order to investigate whether hepatitis B surface S protein (HBs) was able to directly or indirectly promote the proliferation and expression of collagen type I (Col I) and α‑smooth muscle actin (α‑SMA) in hepatic stellate cells (HSCs). The LX‑2 human cell line and the HepG2 human hepatocellular carcinoma cell line were employed as HSCs and as hepatocytes, respectively. Recombinant HBs was added to the LX‑2 cells for 48 h and the cell proliferation was assessed by the MTT assay. Col I and α‑SMA were measured in the supernatant by ELISA, following treatment of the LX‑2 and̸or HepG2 cells with recombinant HBs. Transforming growth factor‑β1 (TGF‑β1) was also determined by ELISA in the HepG2 cell supernatants. The data demonstrated that high concentrations of recombinant HBs (10‑50 ng/ml) inhibited the proliferation of LX‑2 cells, whereas low concentrations (0.5‑5 ng/ml) did not affect LX‑2 cell proliferation. After treating LX‑2 cells alone with recombinant HBs for 48 h, there was no significant increase in the Col I and α‑SMA levels. However, Col I was increased ~1.7‑fold in co‑cultured (LX‑2 and HepG2) cell supernatants following treatment with HBs for 24 h (HBs vs. control group: 48.51±3.51 vs. 28.23±2.55 ng̸ml, respectively). Furthermore, TGF‑β1 was significantly increased in the HepG2 cell supernatants following treatment with recombinant HBs. Therefore, we concluded that HBs directly affected the proliferation of HSCs, but promoted the Col I expression in HSCs possibly by virtue of hepatocytes secreting TGF‑β1. This may provide a novel explanation of the fibrogenetic mechanism induced by hepatitis B virus‑related proteins.

View Figures

View References

1	Ocama P, Opio CK and Lee WM: Hepatitis B virus infection: current status. Am J Med. 118:14132005. View Article : Google Scholar : PubMed/NCBI
2	Lavanchy D: Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 11:97–107. 2004. View Article : Google Scholar : PubMed/NCBI
3	Kao JH and Chen DS: Global control of hepatitis B virus infection. Lancet Infect Dis. 2:395–403. 2002. View Article : Google Scholar : PubMed/NCBI
4	Lee WM: Hepatitis B virus infection. N Engl J Med. 337:1733–1745. 1997. View Article : Google Scholar : PubMed/NCBI
5	Ganem D and Prince AM: Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med. 350:1118–1129. 2004. View Article : Google Scholar : PubMed/NCBI
6	Wright TL: Introduction to chronic hepatitis B infection. Am J Gastroenterol. 101(Suppl 1): S1–S6. 2006. View Article : Google Scholar : PubMed/NCBI
7	Eng FJ and Friedman SL: Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex. Am J Physiol Gastrointest Liver Physiol. 279:G7–G11. 2000.PubMed/NCBI
8	Friedman SL: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 275:2247–2250. 2000. View Article : Google Scholar : PubMed/NCBI
9	Poynard T, Mathurin P, Lai CL, et al: A comparison of fibrosis progression in chronic liver diseases. J Hepatol. 38:257–265. 2003. View Article : Google Scholar : PubMed/NCBI
10	Norton PA, Reis HM, Prince S, et al: Activation of fibronectin gene expression by hepatitis B virus x antigen. J Viral Hepat. 11:332–341. 2004. View Article : Google Scholar : PubMed/NCBI
11	Guo GH, Tan DM, Zhu PA and Liu F: Hepatitis B virus X protein promotes proliferation and upregulates TGF-beta1 and CTGF in human hepatic stellate cell line, LX-2. Hepatobiliary Pancreat Dis Int. 8:59–64. 2009.PubMed/NCBI
12	Martin-Vilchez S, Sanz-Cameno P, Rodriguez-Munoz Y, et al: The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells. Hepatology. 47:1872–1883. 2008. View Article : Google Scholar : PubMed/NCBI
13	Zan Y, Zhang Y and Tien P: Hepatitis B virus e antigen induces activation of rat hepatic stellate cells. Biochem Biophys Res Commun. 435:391–396. 2013. View Article : Google Scholar : PubMed/NCBI
14	Chen HY, Wang XZ and Chen ZX: Expression of the hepatitis B virus X gene in liver cells promotes the proliferation and migration of co-cultured hepatic stellate cells. World Chin J Digestol. 20:721–728. 2012.(In Chinese).
15	Liu X, Zhu ST, You H, Cong M, Liu TH, Wang BE and Jia JD: Hepatitis B virus infects hepatic stellate cells and affects their proliferation and expression of collagen type I. Chin Med J (Engl). 122:1455–1461. 2009.PubMed/NCBI
16	Beasley RP, Shiao IS, Wu TC and Hwang LY: Hepatoma in an HBsAg carrier - seven years after perinatal infection. J Pediatr. 101:83–84. 1982.PubMed/NCBI
17	Lupberger J and Hildt E: Hepatitis B virus-induced oncogenesis. World J Gastroenterol. 13:74–81. 2007. View Article : Google Scholar
18	Chevaliez S: Is HBsAg quantification ready, for prime time? Clin Res Hepatol Gastroenterol. Aug 7–2013.(Epub ahead of print). View Article : Google Scholar
19	Mazzocca A, Sciammetta SC, Carloni V, et al: Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J Biol Chem. 280:11329–11339. 2005. View Article : Google Scholar : PubMed/NCBI
20	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. 54:142–151. 2005. View Article : Google Scholar : PubMed/NCBI
21	Gabele E, Brenner DA and Rippe RA: Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell. Front Biosci. 8:d69–d77. 2003. View Article : Google Scholar : PubMed/NCBI
22	Kato J, Sato Y, Inui N, et al: Ethanol induces transforming growth factor-alpha expression in hepatocytes, leading to stimulation of collagen synthesis by hepatic stellate cells. Alcohol Clin Exp Res. 27(Suppl 8): 58S–63S. 2003. View Article : Google Scholar
23	Parkes JG and Templeton DM: Modulation of stellate cell proliferation and gene expression by rat hepatocytes: effect of toxic iron overload. Toxicol Lett. 144:225–233. 2003. View Article : Google Scholar : PubMed/NCBI
24	Zeisberg M, Yang C, Martino M, et al: Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem. 282:23337–23347. 2007. View Article : Google Scholar : PubMed/NCBI
25	Tseng TC, Liu CJ, Yang HC, et al: Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads. Hepatology. 57:441–450. 2013. View Article : Google Scholar : PubMed/NCBI
26	Martinot-Peignoux M, Lapalus M, Asselah T and Marcellin P: The role of HBsAg quantification for monitoring natural history and treatment outcome. Liver Int. 33(Suppl 1): 125–132. 2013. View Article : Google Scholar : PubMed/NCBI
27	Liao R, Wu H, Yi Y, et al: Clinical significance and gene expression study of human hepatic stellate cells in HBV related-hepatocellular carcinoma. J Exp Clin Cancer Res. 32:222013. View Article : Google Scholar : PubMed/NCBI
28	Greupink R, Bakker HI, Bouma W, et al: The antiproliferative drug doxorubicin inhibits liver fibrosis in bile duct-ligated rats and can be selectively delivered to hepatic stellate cells in vivo. J Pharmacol Exp Ther. 317:514–521. 2006. View Article : Google Scholar : PubMed/NCBI