Skip to main content
Log in

Recombinant T2 RNase protein of Schistosoma japonicum inhibits expression of α-SMA in LX-2 cells

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Recombinant T2 RNase glycoprotein, which showed a certain degree of homology to Omega-1 from Schistosoma mansoni eggs, was expressed in adult worms of Schistosoma japonicum, but not in eggs of S. japonicum. The direct biological role of the recombinant T2 RNase protein in activation of hepatic stellate cells (HSCs) remains unknown. In the present study, the immortalized human HSC line (LX-2 cells) was treated with the recombinant T2 RNase protein at indicated concentrations for various time points in vitro. The expression levels of α-smooth muscle actin (α-SMA) and Smad4 were detected by Western blot. The results showed that the recombinant T2 RNase protein significantly diminished the expression levels of α-SMA and Smad4 in LX-2 cells. The upregulated expression levels of α-SMA and Smad4 by TGF-β1 in LX-2 cells were both suppressed by the recombinant T2 RNase protein. These data suggest that the recombinant T2 RNase protein may be a potential target of therapeutic strategy for the treatment of hepatic fibrosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Anthony B, Mathieson W, de Castro-Borges W, Allen J (2010) Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis. Exp Parasitol 124(4):409–420

    Article  CAS  PubMed  Google Scholar 

  • Anthony BJ, Ramm GA, McManus DP (2012) Role of resident liver cells in the pathogenesis of schistosomiasis. Trends Parasitol 28(12):572–579

    Article  CAS  PubMed  Google Scholar 

  • Anthony BJ, James KR, Gobert GN, Ramm GA, McManus DP (2013) Schistosoma eggs induce a proinflammatory, anti-fibrogenic phenotype in hepatic stellate cells. PLoS One 8(6), e68479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burke ML, Jones MK, Gobert GN, Li YS, Ellis MK, McManus DP (2009) Immunopathogenesis of human schistosomiasis. Parasite Immunol 31(4):163–176

    Article  CAS  PubMed  Google Scholar 

  • Castilho-Fernandes A, de Almeida DC, Fontes AM, Melo FU, Picanco-Castro V, Freitas MC, Orellana MD, Palma PV, Hackett PB, Friedman SL, Covas DT (2011) Human hepatic stellate cell line (LX-2) exhibits characteristics of bone marrow-derived mesenchymal stem cells. Exp Mol Pathol 91(3):664–672

    Article  CAS  PubMed  Google Scholar 

  • Doenhoff MJ, Pearson S, Dunne DW, Bickle Q, Lucas S, Bain J, Musallam R, Hassounah O (1981) Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice. Trans R Soc Trop Med Hyg 75(1):41–53

    Article  CAS  PubMed  Google Scholar 

  • Duan Y, Gu X, Zhu D, Sun W, Chen J, Feng J, Song K, Xu F, He X, He X (2014) Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: a possible molecular mechanism. Int J Parasitol 44(3–4):217–224

    Article  CAS  PubMed  Google Scholar 

  • Dunne DW, Jones FM, Doenhoff MJ (1991) The purification, characterization, serological activity and hepatotoxic properties of two cationic glycoproteins (alpha 1 and omega 1) from Schistosoma mansoni eggs. Parasitology 103(Pt 2):225–236

    Article  CAS  PubMed  Google Scholar 

  • Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, Doenhoff MJ, van der Bosch J, Mohrs K, Haas H, Mohrs M, Yazdanbakhsh M, Schramm G (2009) Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med 206(8):1673–1680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Everts B, Hussaarts L, Driessen NN, Meevissen MH, Schramm G, van der Ham AJ, van der Hoeven B, Scholzen T, Burgdorf S, Mohrs M, Pearce EJ, Hokke CH, Haas H, Smits HH, Yazdanbakhsh M (2012) Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor. J Exp Med 209(10):1753–1767, S1751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng JR, Zhu DD, Qin YW, Sun W, Zhuang Z, Duan YN (2013) Expression and activity analysis of a kind of T2 Rnase from Schistosoma japonicum. Chinese J Zoonoses 29(11):1039–1043

    CAS  Google Scholar 

  • Ferguson BJ, Newland SA, Gibbs SE, Tourlomousis P, Fernandes Dos Santos P, Patel MN, Hall SW, Walczak H, Schramm G, Haas H, Dunne DW, Cooke A, Zaccone P (2015) The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1beta secretion in macrophages. Int J Parasitol 45(13):809–813

    Article  CAS  PubMed  Google Scholar 

  • Fitzsimmons CM, Schramm G, Jones FM, Chalmers IW, Hoffmann KF, Grevelding CG, Wuhrer M, Hokke CH, Haas H, Doenhoff MJ, Dunne DW (2005) Molecular characterization of omega-1: a hepatotoxic ribonuclease from Schistosoma mansoni eggs. Mol Biochem Parasitol 144(1):123–127

    Article  CAS  PubMed  Google Scholar 

  • Hagen J, Young ND, Every AL, Pagel CN, Schnoeller C, Scheerlinck JP, Gasser RB, Kalinna BH (2014) Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo. Nat Commun 5:5375

    Article  PubMed  PubMed Central  Google Scholar 

  • He W, Dai C (2015) Key fibrogenic signaling. Curr Pathobiol Rep 3(2):183–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamato D, Burch ML, Piva TJ, Rezaei HB, Rostam MA, Xu S, Zheng W, Little PJ, Osman N (2013) Transforming growth factor-beta signalling: role and consequences of Smad linker region phosphorylation. Cell Signal 25(10):2017–2024

    Article  CAS  PubMed  Google Scholar 

  • Ke XD, Yu CX, Song LJ, Mihoko K, Hirayama K, Wang J, Yin XR, Jin Y, Shen S, Yao Y, Gao H, Gao Q (2013) Expression and characterization of RNase-T2 of Schistosoma japonicum. J Patho Biol 8(12):1082–1088

    Google Scholar 

  • Khanizadeh S, Ravanshad M, Hosseini S, Davoodian P, Nejati Zadeh A, Sarvari J (2015) Blocking of SMAD4 expression by shRNA effectively inhibits fibrogenesis of human hepatic stellate cells. Gastroenterol Hepatol Bed Bench 8(4):262–269

    PubMed  PubMed Central  Google Scholar 

  • Lee UE, Friedman SL (2011) Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 25(2):195–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luhtala N, Parker R (2010) T2 family ribonucleases: ancient enzymes with diverse roles. Trends Biochem Sci 35(5):253–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morishita Y, Yoshizawa H, Watanabe M, Ishibashi K, Muto S, Kusano E, Nagata D (2014) siRNAs targeted to Smad4 prevent renal fibrosis in vivo. Sci Rep 4:6424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moustakas A, Heldin CH (2009) The regulation of TGFbeta signal transduction. Development 136(22):3699–3714

    Article  CAS  PubMed  Google Scholar 

  • Pinzani M, Marra F (2001) Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 21(3):397–416

    Article  CAS  PubMed  Google Scholar 

  • Song LG, Wu ZD (2015) Pathology and pathogenesis of liver fibrosis induced by Schistosoma japonicum. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 27(2):213–216, 220

    PubMed  Google Scholar 

  • Steinfelder S, Andersen JF, Cannons JL, Feng CG, Joshi M, Dwyer D, Caspar P, Schwartzberg PL, Sher A, Jankovic D (2009) The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1). J Exp Med 206(8):1681–1690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suarez-Cuenca JA, Chagoya De Sanchez V, Aranda-Fraustro A, Sanchez-Sevilla L, Martinez-Perez L, Hernandez-Munoz R (2008) Partial hepatectomy-induced regeneration accelerates reversion of liver fibrosis involving participation of hepatic stellate cells. Exp Biol Med (Maywood) 233(7):827–839

    Article  CAS  Google Scholar 

  • Sun X, Zhang L, Wang J, Chen J, Zhu D, Shen P, He X, Pan J, Peng W, Duan Y (2015) Schistosoma japonicum protein SjP40 inhibits TGF-beta1-induced activation of hepatic stellate cells. Parasitol Res 114(11):4251–4257

    Article  PubMed  Google Scholar 

  • Tu X, Zhang H, Zhang J, Zhao S, Zheng X, Zhang Z, Zhu J, Chen J, Dong L, Zang Y (2014) MicroRNA-101 suppresses liver fibrosis by targeting the TGFbeta signalling pathway. J Pathol 234(1):46–59

    Article  CAS  PubMed  Google Scholar 

  • Tu X, Zheng X, Li H, Cao Z, Chang H, Luan S, Zhu J, Chen J, Zang Y, Zhang J (2015) MicroRNA-30 protects against carbon tetrachloride-induced liver fibrosis by attenuating transforming growth factor beta signaling in hepatic stellate cells. Toxicol Sci 146(1):157–169

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Xu F, Zhu D, Duan Y, Chen J, Sun X, He X, Li P, Sun W, Feng J (2014) Schistosoma japonicum soluble egg antigens facilitate hepatic stellate cell apoptosis by downregulating Akt expression and upregulating p53 and DR5 expression. PLoS Negl Trop Dis 8(8), e3106

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu L, Hui AY, Albanis E, Arthur MJ, O’Byrne SM, Blaner WS, Mukherjee P, Friedman SL, Eng FJ (2005) Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 54(1):142–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou XH, Wu JY, Huang XQ, Kunnon SP, Zhu XQ, Chen XG (2010) Identification and characterization of Schistosoma japonicum Sjp40, a potential antigen candidate for the early diagnosis of schistosomiasis. Diagn Microbiol Infect Dis 67(4):337–345

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81471975, 81171589, 81501763, and 81401683), the Jiangsu Provincial Natural Science Foundation (Grant Number BK20140435), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Shaoqing Ju or Yinong Duan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Jianxin Wang, Wenxia Peng and Jinrong Feng contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Peng, W., Feng, J. et al. Recombinant T2 RNase protein of Schistosoma japonicum inhibits expression of α-SMA in LX-2 cells. Parasitol Res 115, 4055–4060 (2016). https://doi.org/10.1007/s00436-016-5178-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-016-5178-z

Keywords

Navigation