Expression of recombinant Schistosoma japonicum protein rSjE16 and its effects on LX-2 cells in vitro

Objective The activation of hepatic stellate cells (HSCs) is a key event in schistosome-induced liver fibrosis. Previous studies have shown that soluble egg antigens and the recombinant P40 protein from Schistosoma japonicum eggs inhibit HSC activation. In the present study, we observed the direct effect of the S. japonicum recombinant (r)SjE16 protein on HSCs. Methods The sequence of SjE16 was analyzed by bioinformatics. Then western blotting, quantitative PCR, and MTT assays were performed to observe the effects of rSjE16 on HSCs. Results The SjE16 protein has no signal peptide or transmembrane region. rSjE16 significantly inhibited expression levels of α-smooth muscle actin and collagen I protein in LX-2 cells. rSjE16 also significantly increased the expression levels of interleukin (IL)-6 and IL-8, and enhanced the expression of matrix metalloproteinase (MMP)-2, MMP-9, and peroxisome proliferator-activated receptor-γ in LX-2 cells. LX-2 cell viability was not inhibited by rSjE16. Conclusion rSjE16 may be involved in the progression of HSC activation via a complex molecular mechanism, which requires further study to fully understand.

[1]  S. Ju,et al.  Recombinant T2 RNase protein of Schistosoma japonicum inhibits expression of α-SMA in LX-2 cells , 2016, Parasitology Research.

[2]  V. Lagente,et al.  Characterization of the MMP/TIMP Imbalance and Collagen Production Induced by IL-1β or TNF-α Release from Human Hepatic Stellate Cells , 2016, PloS one.

[3]  Yang Yang,et al.  SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development. , 2015, Acta tropica.

[4]  Jing-kun Pan,et al.  Schistosoma japonicum protein SjP40 inhibits TGF-β1-induced activation of hepatic stellate cells , 2015, Parasitology Research.

[5]  Zhong-dao Wu,et al.  [Pathology and pathogenesis of liver fibrosis induced by Schistosoma japonicum]. , 2015, Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control.

[6]  R. Weiskirchen,et al.  Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities. , 2015, Biochemical and biophysical research communications.

[7]  D. McManus,et al.  Defining a pro‐inflammatory neutrophil phenotype in response to schistosome eggs , 2014, Cellular microbiology.

[8]  Feifan Xu,et al.  Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: a possible molecular mechanism. , 2014, International journal for parasitology.

[9]  Yang Yang,et al.  Schistosoma japonicum Egg Specific Protein SjE16.7 Recruits Neutrophils and Induces Inflammatory Hepatic Granuloma Initiation , 2014, PLoS neglected tropical diseases.

[10]  S. Friedman,et al.  Hepatic stellate cells and liver fibrosis. , 2013, Comprehensive Physiology.

[11]  D. McManus,et al.  Schistosoma japonicum Eggs Induce a Proinflammatory, Anti-Fibrogenic Phenotype in Hepatic Stellate Cells , 2013, PloS one.

[12]  Yan Feng,et al.  [Eukaryotic expression of SjE16, SjPPIase and SjRobl genes from Schistosoma japonicum egg and evaluation of their role in immunodiagnosis]. , 2013, Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases.

[13]  P. Fallon,et al.  The Schistosoma Granuloma: Friend or Foe? , 2013, Front. Immunol..

[14]  Qiyu Zhang,et al.  Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6. , 2012, World journal of gastroenterology.

[15]  Yuesheng Li,et al.  A Role for Peroxisome Proliferator-Activated Receptors in the Immunopathology of Schistosomiasis? , 2011, PPAR research.

[16]  S. Friedman,et al.  Loss of Matrix Metalloproteinase-2 Amplifies Murine Toxin-Induced Liver Fibrosis by Upregulating Collagen I Expression , 2011, Digestive Diseases and Sciences.

[17]  Jun Yu,et al.  Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro. , 2010, The international journal of biochemistry & cell biology.

[18]  Jeremy T. Allen,et al.  Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis. , 2010, Experimental parasitology.

[19]  J. Iredale,et al.  Active matrix metalloproteinase‐2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N‐cadherin , 2009, Liver international : official journal of the International Association for the Study of the Liver.

[20]  Z. Andrade.  Schistosomiasis and hepatic fibrosis regression. , 2008, Acta tropica.

[21]  D. Brenner,et al.  Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis , 2007, Journal of gastroenterology and hepatology.

[22]  Yuanping Han.  Matrix metalloproteinases, the pros and cons, in liver fibrosis , 2006, Journal of gastroenterology and hepatology.

[23]  Luc Kestens,et al.  Human schistosomiasis , 2006, The Lancet.

[24]  H. Tsukamoto,et al.  Anti‐adipogenic regulation underlies hepatic stellate cell transdifferentiation , 2006, Journal of gastroenterology and hepatology.

[25]  D. Burggraf,et al.  Matrix metalloproteinase‐9 promotes neutrophil and T cell recruitment and migration in the postischemic liver , 2006, Journal of leukocyte biology.

[26]  Zhu Chen,et al.  New Perspectives on Host-Parasite Interplay by Comparative Transcriptomic and Proteomic Analyses of Schistosoma japonicum , 2006, PLoS pathogens.

[27]  Li-juan Zhang,et al.  Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats. , 2006, World journal of gastroenterology.

[28]  S. Friedman,et al.  Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis , 2004, Gut.

[29]  L. Drake,et al.  DYNAMICS OF THE CYTOKINE MESSENGER RNA EXPRESSION PATTERN IN THE LIVER OF BABOONS INFECTED WITH SCHISTOSOMA MANSONI , 2004, The Journal of parasitology.

[30]  Feng Liu,et al.  Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource , 2003, Nature Genetics.

[31]  F. Marra,et al.  Cytokine Receptors and Signaling in Hepatic Stellate Cells , 2001, Seminars in liver disease.

[32]  E. Pearce,et al.  Role of IL-6 in Directing the Initial Immune Response to Schistosome Eggs1 , 2000, The Journal of Immunology.

[33]  Gennaro Ciliberto,et al.  Increased toxin‐induced liver injury and fibrosis in interleukin‐6–deficient mice , 2000, Hepatology.

[34]  D. Moser,et al.  A stage-specific calcium-binding protein expressed in eggs of Schistosoma mansoni. , 1992, Molecular and biochemical parasitology.

[35]  H. Tsukamoto,et al.  Stimulation of hepatic lipocyte collagen production by Kupffer cell‐derived transforming growth factor β: Implication for a pathogenetic role in alcoholic liver fibrogenesis , 1990, Hepatology.

[36]  M. Yáñez,et al.  Calcium binding proteins. , 2012, Advances in experimental medicine and biology.

[37]  Wei Hu,et al.  [Prokaryotic expression of gene encoding Schistosoma japonicum SjE16 and its potential application in immunodiagnosis]. , 2003, Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases.

[38]  M. Válková.  Hepatic fibrogenesis. , 2002, Bratislavske lekarske listy.