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Tissue Transglutaminase-Regulated Transformed Growth Factor-?1 in the Parasite
Links Schistosoma japonicum Infection with Liver Fibrosis
#MMPMID26199461
Tang J
; Zhu X
; Zhao J
; Fung M
; Li Y
; Gao Z
; Yan S
; Li X
; Ji X
; Su F
; Li Z
Mediators Inflamm
2015[]; 2015
(?): 659378
PMID26199461
show ga
Transforming growth factor (TGF-?1) 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-?1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to
explore the consistency between tTG and TGF-?1 and TGF-?1 source and its
correlation with liver fibrosis after Sj-infection. TGF-?1 was upregulated at
weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-?1 level
decreased in sera and liver of infected mice. TGF-?1 showed positive staining in
liver containing Sj adult worms and eggs. TGF-?1 was also detected in Sj adult
worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms'
culture medium. The TGF-?1 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-?1
transcript in Sj eggs was higher than in adult worms. In Sj-infected liver,
transcriptional level of TGF-?1 from Sj, but not mouse liver, correlated with
liver fibrosis extent. This study provides evidence that tTG regulates TGF-?1 and
illustrates the importance of targeting tTG in treating Sj infection-induced
fibrosis.
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