Skip to main content
Erschienen in: Archives of Virology 12/2013

01.12.2013 | Original Article

Effects of hepatitis B virus X gene on apoptosis and expression of immune molecules of human proximal tubular epithelial cells

verfasst von: Xuan Wang, Yi Zhou, Nan Zhu, Wei-jie Yuan

Erschienen in: Archives of Virology | Ausgabe 12/2013

Einloggen, um Zugang zu erhalten

Abstract

The hepatitis B virus X protein (HBx) is the most important determinant in viral pathogenesis. HBx regulates HBV replication, cellular transcription, signal transduction, proteasome activity and cell cycle progression. In this study, HK-2 cells were transiently transfected with the HBx gene using a eukaryotic vector, pcDNA3.1/myc-HBx. Transfection with the HBx gene increased the number of apoptotic cells. In addition, cultured HK-2 cells became irregular in shape. The expression of α-SMA and E-cadherin, TLR4, MHC-II and CD40 was increased. The transfection resulted in increased IL-1, IL-6, TNF-α and IFN-γ levels in the supernatant and decreased IL-4 in the supernatant. In conclusion, overexpression of the HBx gene in renal tubular epithelial cells induces apoptosis of HK-2 cells and promotes epithelial-mesenchymal transdifferentiation. HBx transfection upregulates the expression of immune molecules in renal tubular epithelial cells and induces an imbalance in cytokine levels.
Literatur
1.
Zurück zum Zitat Yi Z, Jie YW, Nan Z (2011) The efficacy of anti-viral therapy of hepatitis B virus-associated membranous glomerulonephritis: a systematic review and meta-analysis. Ann Hepatol 10:165–173PubMed Yi Z, Jie YW, Nan Z (2011) The efficacy of anti-viral therapy of hepatitis B virus-associated membranous glomerulonephritis: a systematic review and meta-analysis. Ann Hepatol 10:165–173PubMed
2.
Zurück zum Zitat Takekoshi Y, Tochimaru H, Nagata Y, Itami N (1991) Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy. Kidney Int Suppl 35:S34–S39PubMed Takekoshi Y, Tochimaru H, Nagata Y, Itami N (1991) Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy. Kidney Int Suppl 35:S34–S39PubMed
3.
Zurück zum Zitat Chen L, Wu C, Fan X, Gao J, Yin H, Wang T, Wu J, Wen SW (2009) Replication and infectivity of hepatitis B virus in HBV-related glomerulonephritis. Int J Infect Dis 13:394–398PubMedCrossRef Chen L, Wu C, Fan X, Gao J, Yin H, Wang T, Wu J, Wen SW (2009) Replication and infectivity of hepatitis B virus in HBV-related glomerulonephritis. Int J Infect Dis 13:394–398PubMedCrossRef
4.
Zurück zum Zitat Bhimma R, Coovadia HM (2004) Hepatitis B virus-associated nephropathy. Am J Nephrol 24:198–211PubMedCrossRef Bhimma R, Coovadia HM (2004) Hepatitis B virus-associated nephropathy. Am J Nephrol 24:198–211PubMedCrossRef
5.
Zurück zum Zitat Murakami S (2001) Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol 36:651–660PubMedCrossRef Murakami S (2001) Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol 36:651–660PubMedCrossRef
6.
Zurück zum Zitat Bouchard MJ, Schneider RJ (2004) The enigmatic X gene of hepatitis B virus. J Virol 8:12725–12734CrossRef Bouchard MJ, Schneider RJ (2004) The enigmatic X gene of hepatitis B virus. J Virol 8:12725–12734CrossRef
7.
Zurück zum Zitat Kim CM, Koike K, Saito I, Miyamura T, Jay G (1991) HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351:317–320PubMedCrossRef Kim CM, Koike K, Saito I, Miyamura T, Jay G (1991) HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351:317–320PubMedCrossRef
8.
Zurück zum Zitat Xu J, Yun X, Jiang J, Wei Y, Wu Y, Zhang W, Liu Y, Wang W, Wen Y, Gu J (2010) Hepatitis B virus X protein blunts senescence-like growth arrest of human hepatocellular carcinoma by reducing Notch1 cleavage. Hepatology 52:142–154PubMedCrossRef Xu J, Yun X, Jiang J, Wei Y, Wu Y, Zhang W, Liu Y, Wang W, Wen Y, Gu J (2010) Hepatitis B virus X protein blunts senescence-like growth arrest of human hepatocellular carcinoma by reducing Notch1 cleavage. Hepatology 52:142–154PubMedCrossRef
9.
Zurück zum Zitat Kim WH, Hong F, Jaruga B, Zhang ZS, Fan SJ, Liang TJ, Gao B (2005) Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism. Cell Mol Immunol 2:40–48PubMed Kim WH, Hong F, Jaruga B, Zhang ZS, Fan SJ, Liang TJ, Gao B (2005) Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism. Cell Mol Immunol 2:40–48PubMed
10.
Zurück zum Zitat Liang X, Liu Y, Zhang Q, Gao L, Han L, Ma C, Zhang L, Chen YH, Sun W (2007) Hepatitis B virus sensitizes hepatocytes to TRAIL-induced apoptosis through Bax. J Immunol 178:503–510PubMed Liang X, Liu Y, Zhang Q, Gao L, Han L, Ma C, Zhang L, Chen YH, Sun W (2007) Hepatitis B virus sensitizes hepatocytes to TRAIL-induced apoptosis through Bax. J Immunol 178:503–510PubMed
11.
Zurück zum Zitat Hu L, Chen L, Yang G, Li L, Sun H, Chang Y, Tu Q, Wu M, Wang H (2011) HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade. Mol Cancer 10:43PubMedCrossRef Hu L, Chen L, Yang G, Li L, Sun H, Chang Y, Tu Q, Wu M, Wang H (2011) HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade. Mol Cancer 10:43PubMedCrossRef
12.
Zurück zum Zitat Clippinger AJ, Gearhart TL, Bouchard MJ (2009) Hepatitis B virus X protein modulates apoptosis in primary rat hepatocytes by regulating both NF-kappaB and the mitochondrial permeability transition pore. J Virol 83:4718–4731PubMedCrossRef Clippinger AJ, Gearhart TL, Bouchard MJ (2009) Hepatitis B virus X protein modulates apoptosis in primary rat hepatocytes by regulating both NF-kappaB and the mitochondrial permeability transition pore. J Virol 83:4718–4731PubMedCrossRef
13.
Zurück zum Zitat Lara-Pezzi E, Majano PL, Gómez-Gonzalo M, Garcia-Monzón C, Moreno-Otero R, Levrero M, López-Cabrera M (1998) The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes. Hepatology 28:1013–1021PubMedCrossRef Lara-Pezzi E, Majano PL, Gómez-Gonzalo M, Garcia-Monzón C, Moreno-Otero R, Levrero M, López-Cabrera M (1998) The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes. Hepatology 28:1013–1021PubMedCrossRef
14.
Zurück zum Zitat Lee MJ, Jin YH, Kim K, Choi Y, Kim HC, Park S (2010) Expression of hepatitis B virus x protein in hepatocytes suppresses CD8+T cell activity. Immune Net 10:126–134CrossRef Lee MJ, Jin YH, Kim K, Choi Y, Kim HC, Park S (2010) Expression of hepatitis B virus x protein in hepatocytes suppresses CD8+T cell activity. Immune Net 10:126–134CrossRef
15.
Zurück zum Zitat Xiang WQ, Feng WF, Ke W, Sun Z, Chen Z, Liu W (2011) Hepatitis B virus X protein stimulates IL-6 expression in hepatocytes via a MyD88-dependent pathway. J Hepatol 54:26–33PubMedCrossRef Xiang WQ, Feng WF, Ke W, Sun Z, Chen Z, Liu W (2011) Hepatitis B virus X protein stimulates IL-6 expression in hepatocytes via a MyD88-dependent pathway. J Hepatol 54:26–33PubMedCrossRef
16.
Zurück zum Zitat Han J, Yoo HY, Choi BH, Roh HM (2000) Selective transcriptional regulations in the human liver cell by hepatitis B viral X protein. Biochem Biophys Res Commun 272:525–530PubMedCrossRef Han J, Yoo HY, Choi BH, Roh HM (2000) Selective transcriptional regulations in the human liver cell by hepatitis B viral X protein. Biochem Biophys Res Commun 272:525–530PubMedCrossRef
17.
Zurück zum Zitat Zhou DX, Taraboulos A, Ou JH, Yen TS (1990) Activation of class I major histocompatibility complex gene expression by hepatitis B virus. J Virol 64:4025–4028PubMed Zhou DX, Taraboulos A, Ou JH, Yen TS (1990) Activation of class I major histocompatibility complex gene expression by hepatitis B virus. J Virol 64:4025–4028PubMed
18.
Zurück zum Zitat Hu KQ, Yu CH, Vierling JM (1992) Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein. Proc Natl Acad Sci USA 89:11441–11445PubMedCrossRef Hu KQ, Yu CH, Vierling JM (1992) Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein. Proc Natl Acad Sci USA 89:11441–11445PubMedCrossRef
19.
Zurück zum Zitat He P, Zhang D, Li H, Yang X, Li D, Zhai Y, Ma L, Feng G (2013) Hepatitis B virus X protein modulates apoptosis in human renal proximal tubular epithelial cells by activating the JAK2/STAT3 signaling pathway. Int J Mol Med. doi:10.3892/ijmm.2013.1295 He P, Zhang D, Li H, Yang X, Li D, Zhai Y, Ma L, Feng G (2013) Hepatitis B virus X protein modulates apoptosis in human renal proximal tubular epithelial cells by activating the JAK2/STAT3 signaling pathway. Int J Mol Med. doi:10.​3892/​ijmm.​2013.​1295
20.
Zurück zum Zitat Zhou Y, Zhu N, Wang X, Wang L, Gu LJ, Yuan WJ (2013) The role of the toll-like receptor TLR4 in hepatitis B virus-associated glomerulonephritis. Arch Virol 158:425–433PubMedCrossRef Zhou Y, Zhu N, Wang X, Wang L, Gu LJ, Yuan WJ (2013) The role of the toll-like receptor TLR4 in hepatitis B virus-associated glomerulonephritis. Arch Virol 158:425–433PubMedCrossRef
21.
Zurück zum Zitat Biancone L, Deambrosis I, Camussi G (2002) Lymphocyte costimulatory receptors in renal disease and transplantation. J Nephrol 15:7–16PubMed Biancone L, Deambrosis I, Camussi G (2002) Lymphocyte costimulatory receptors in renal disease and transplantation. J Nephrol 15:7–16PubMed
22.
Zurück zum Zitat Chen Y, Zhang J, Li J, Zou L, Zhao T, Tang Y, Wu Y (2006) Expression of B7–H1 in inflammatory renal tubular epithelial cells. Nephron Exp Nephrol 102:e81–e92PubMedCrossRef Chen Y, Zhang J, Li J, Zou L, Zhao T, Tang Y, Wu Y (2006) Expression of B7–H1 in inflammatory renal tubular epithelial cells. Nephron Exp Nephrol 102:e81–e92PubMedCrossRef
23.
Zurück zum Zitat Qi W, Chen X, Gilbert RE, Zhang Y, Waltham M, Schache M, Kelly DJ, Pollock CA (2007) High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Am J Pathol 171:744–754PubMedCrossRef Qi W, Chen X, Gilbert RE, Zhang Y, Waltham M, Schache M, Kelly DJ, Pollock CA (2007) High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Am J Pathol 171:744–754PubMedCrossRef
24.
Zurück zum Zitat Wan J, Zhou X, Cui J, Zou Z, Xu Y, You D (2012) Role of complement 3 in TNF-α-induced mesenchymal transition of renal tubular epithelial cells in vitro. Mol Biotechnol. doi:10.1007/s12033-012-9547-2 Wan J, Zhou X, Cui J, Zou Z, Xu Y, You D (2012) Role of complement 3 in TNF-α-induced mesenchymal transition of renal tubular epithelial cells in vitro. Mol Biotechnol. doi:10.​1007/​s12033-012-9547-2
25.
Zurück zum Zitat Ho MY, Tang SJ, Chuang MJ, Cha TL, Li JY, Sun GH, Sun HK (2012) TNF-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a GSK3β-dependent mechanism. Mol Cancer Res 10:1109–1119PubMedCrossRef Ho MY, Tang SJ, Chuang MJ, Cha TL, Li JY, Sun GH, Sun HK (2012) TNF-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a GSK3β-dependent mechanism. Mol Cancer Res 10:1109–1119PubMedCrossRef
26.
Zurück zum Zitat Jung TY, Pham TN, Umeyama A, Shoji N, Hashimoto T, Lee JJ, Takei M (2010) Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells. Eur J Pharmacol 643:297–303PubMedCrossRef Jung TY, Pham TN, Umeyama A, Shoji N, Hashimoto T, Lee JJ, Takei M (2010) Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells. Eur J Pharmacol 643:297–303PubMedCrossRef
27.
Zurück zum Zitat Lin CY, Lin CC, Chang GJ, King CC (1997) Defect of cell-mediated immune response against hepatitis B virus: an indication for pathogenesis of hepatitis-B-virus-associated membranous nephropathy. Nephron 76:176–185PubMedCrossRef Lin CY, Lin CC, Chang GJ, King CC (1997) Defect of cell-mediated immune response against hepatitis B virus: an indication for pathogenesis of hepatitis-B-virus-associated membranous nephropathy. Nephron 76:176–185PubMedCrossRef
28.
Zurück zum Zitat Huang J, Kwong J, Sun EC, Liang TJ (1996) Proteosome complex as a potential cellular target of hepatitis B virus X protein. J Virol 70:5582–5591PubMed Huang J, Kwong J, Sun EC, Liang TJ (1996) Proteosome complex as a potential cellular target of hepatitis B virus X protein. J Virol 70:5582–5591PubMed
29.
Zurück zum Zitat Terradillos O, de La Coste A, Pollicino T, Neuveut C, Sitterlin D, Lecoeur H, Gougeon ML, Kahn A, Buendia MA (2002) The hepatitis B virus X protein abrogates Bcl-2-mediated protection against Fas apoptosis in the liver. Oncogene 21:377–386PubMedCrossRef Terradillos O, de La Coste A, Pollicino T, Neuveut C, Sitterlin D, Lecoeur H, Gougeon ML, Kahn A, Buendia MA (2002) The hepatitis B virus X protein abrogates Bcl-2-mediated protection against Fas apoptosis in the liver. Oncogene 21:377–386PubMedCrossRef
30.
Zurück zum Zitat Lee AT, Ren J, Wong ET, Ban KH, Lee LA, Lee CG (2005) The Hepatitis B virus X protein wensitizes HepG2 cells to UV light-induced DNA damage. J Biol Chem 280:33525–33535PubMedCrossRef Lee AT, Ren J, Wong ET, Ban KH, Lee LA, Lee CG (2005) The Hepatitis B virus X protein wensitizes HepG2 cells to UV light-induced DNA damage. J Biol Chem 280:33525–33535PubMedCrossRef
31.
Zurück zum Zitat Hong L, Zhang J, Min J, Lu J, Li F, Li H, Guo S, Li Q (2010) A role for MHBst167/HBX in hepatitis B virus-induced renal tubular cell apoptosis. Nephrol Dial Transplant 25:2125–2133PubMedCrossRef Hong L, Zhang J, Min J, Lu J, Li F, Li H, Guo S, Li Q (2010) A role for MHBst167/HBX in hepatitis B virus-induced renal tubular cell apoptosis. Nephrol Dial Transplant 25:2125–2133PubMedCrossRef
32.
Zurück zum Zitat Wu ST, Sun GH, Hu CY, Huang CS, Wu YH, Wang HH, Sun. KH (2011) Tumor necrosis factor-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a nuclear factor kappa B-independent mechanism. Exp Biol Med (Maywood) 236:1022–1029 Wu ST, Sun GH, Hu CY, Huang CS, Wu YH, Wang HH, Sun. KH (2011) Tumor necrosis factor-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a nuclear factor kappa B-independent mechanism. Exp Biol Med (Maywood) 236:1022–1029
33.
Zurück zum Zitat Morishita Y, Watanabe M, Nakazawa E, Ishibashi K, Kusano E (2011) The interaction of LFA-1 on mononuclear cells and ICAM-1 on tubular epithelial cells accelerates TGF-β1-induced renal epithelial-mesenchymal transition. PloS One 6:e23267PubMedCrossRef Morishita Y, Watanabe M, Nakazawa E, Ishibashi K, Kusano E (2011) The interaction of LFA-1 on mononuclear cells and ICAM-1 on tubular epithelial cells accelerates TGF-β1-induced renal epithelial-mesenchymal transition. PloS One 6:e23267PubMedCrossRef
34.
Zurück zum Zitat Chen Y, Zhang J, Li J, Zhao T, Zou L, Tang Y, Zhang X, Wu Y (2006) Triptolide inhibits B7–H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-κB transcription. Mol Immunol 43:1088–1098PubMedCrossRef Chen Y, Zhang J, Li J, Zhao T, Zou L, Tang Y, Zhang X, Wu Y (2006) Triptolide inhibits B7–H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-κB transcription. Mol Immunol 43:1088–1098PubMedCrossRef
35.
Zurück zum Zitat Wahl P, Wüthrich RP (2004) Role of the B7RP-1/ICOS pathway in renal tubular epithelial antigen presentation to CD4+ Th1 and Th2 cells. Nephron Exp Nephrol 98:e31–e38PubMedCrossRef Wahl P, Wüthrich RP (2004) Role of the B7RP-1/ICOS pathway in renal tubular epithelial antigen presentation to CD4+ Th1 and Th2 cells. Nephron Exp Nephrol 98:e31–e38PubMedCrossRef
36.
Zurück zum Zitat Tsuboi N, Yoshikai Y, Matsuo S, Kikuchi T, Iwami K, Nagai Y, Takeuchi O, Akira S, Matsuguchi T (2002) Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J Immunol 169:2026–2033PubMed Tsuboi N, Yoshikai Y, Matsuo S, Kikuchi T, Iwami K, Nagai Y, Takeuchi O, Akira S, Matsuguchi T (2002) Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J Immunol 169:2026–2033PubMed
37.
Zurück zum Zitat Lian JQ, Wang XQ, Zhang Y, Huang CX, Bai XF (2009) Correlation of circulating TLR2/4 expression with CD3+/4+/8+ T cells and Treg cells in HBV-related liver cirrhosis. Viral Immunol 22:301–308PubMedCrossRef Lian JQ, Wang XQ, Zhang Y, Huang CX, Bai XF (2009) Correlation of circulating TLR2/4 expression with CD3+/4+/8+ T cells and Treg cells in HBV-related liver cirrhosis. Viral Immunol 22:301–308PubMedCrossRef
38.
Zurück zum Zitat Barton GM, Medzhitov R (2002) Toll-like receptors and their ligands. Curr Top Microbiol Immunol 270:81–92PubMedCrossRef Barton GM, Medzhitov R (2002) Toll-like receptors and their ligands. Curr Top Microbiol Immunol 270:81–92PubMedCrossRef
39.
Zurück zum Zitat Yu Y, Wu H, Tang Z, Zang G (2009) CTLA4 silencing with siRNA promotes deviation of Th1/Th2 in chronic hepatitis B patients. Cell Mol Immunol 6:123–127PubMedCrossRef Yu Y, Wu H, Tang Z, Zang G (2009) CTLA4 silencing with siRNA promotes deviation of Th1/Th2 in chronic hepatitis B patients. Cell Mol Immunol 6:123–127PubMedCrossRef
Metadaten
Titel
Effects of hepatitis B virus X gene on apoptosis and expression of immune molecules of human proximal tubular epithelial cells
verfasst von
Xuan Wang
Yi Zhou
Nan Zhu
Wei-jie Yuan
Publikationsdatum
01.12.2013
Verlag
Springer Vienna
Erschienen in
Archives of Virology / Ausgabe 12/2013
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-013-1759-7

Weitere Artikel der Ausgabe 12/2013

Archives of Virology 12/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.