title: Tissue Transglutaminase-Regulated Transformed Growth Factor-β1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.
abstract: Transforming growth factor (TGF-β1) is among the strongest factors of liver fibrogenesis, but its association with Schistosoma-caused liver fibrosis is controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling TGF-β1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to explore the consistency between tTG and TGF-β1 and TGF-β1 source and its correlation with liver fibrosis after Sj-infection. TGF-β1 was upregulated at weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-β1 level decreased in sera and liver of infected mice. TGF-β1 showed positive staining in liver containing Sj adult worms and eggs. TGF-β1 was also detected in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms' culture medium. The TGF-β1 mature peptide cDNA sequence and its extended sequence were amplified through RT-PCR and RACE-PCR using adult worms as template, and sequence is analyzed and loaded to NCBI GenBank (number GQ338152.1). TGF-β1 transcript in Sj eggs was higher than in adult worms. In Sj-infected liver, transcriptional level of TGF-β1 from Sj, but not mouse liver, correlated with liver fibrosis extent. This study provides evidence that tTG regulates TGF-β1 and illustrates the importance of targeting tTG in treating Sj infection-induced fibrosis.
authors.affiliation: Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Morphology Department, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Xunmin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Mingchiu
authors.initials: M
authors.lastname: Fung
authors.affiliation: Morphology Department, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Morphology Department, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Morphology Department, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Suikai
authors.initials: S
authors.lastname: Yan
authors.affiliation: Morphology Department, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Li
authors.affiliation: Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ji
authors.affiliation: Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Su
authors.affiliation: Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012549:Schistosoma japonicum / Q000472:pathogenicity*; D012554:Schistosomiasis japonica / Q000097:blood* / Q000378:metabolism / Q000469:parasitology; D053773:Transforming Growth Factor beta1 / Q000097:blood* / Q000378:metabolism*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins