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Tissue Transglutaminase-Regulated Transformed Growth Factor-β1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

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)

Bottom Line: During tTG inhibition, TGF-β1 level decreased in sera and liver of infected mice.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.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.

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.

No MeSH data available.


Related in: MedlinePlus

TGF-β1 is transcribed in Sj and Sj-infected mouse liver. Equal amounts of total RNA from left lobes of BALB/c mice liver with 20 ± 3 infective cercariae of Sj for 5, 6, 8, and 12 weeks were detected for TGF-β1 mRNA expression in Sj by using PCR (a) and SYBR Green-based quantitative PCR (b). Sj tubulin-α was detected as an input control. ∗P < 0.05, ∗∗P < 0.01. (c) Equal amounts of total RNA from infected mice livers at indicated time points were detected for mouse TGF-β1 mRNA expression by SYBR Green-based quantitative PCR. GAPDH was detected as an input control. ∗P < 0.05, ∗∗P < 0.01.
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fig5: TGF-β1 is transcribed in Sj and Sj-infected mouse liver. Equal amounts of total RNA from left lobes of BALB/c mice liver with 20 ± 3 infective cercariae of Sj for 5, 6, 8, and 12 weeks were detected for TGF-β1 mRNA expression in Sj by using PCR (a) and SYBR Green-based quantitative PCR (b). Sj tubulin-α was detected as an input control. ∗P < 0.05, ∗∗P < 0.01. (c) Equal amounts of total RNA from infected mice livers at indicated time points were detected for mouse TGF-β1 mRNA expression by SYBR Green-based quantitative PCR. GAPDH was detected as an input control. ∗P < 0.05, ∗∗P < 0.01.

Mentions: To gain a better understanding of the source of TGF-β1 in hepatic fibrogenesis, the transcriptional levels of TGF-β1 in mice and Sj were evaluated using RT-PCR and SYBR Green quantitative PCR. Sj-infected mouse liver cDNA was prepared as a PCR template, and the specific primer pairs shown in Figure 4(a) were also used. TGF-β1 mRNA expression level in Sj increased, especially at week 8 (Figures 5(a) and 5(b)), and this level was comparable with the TGF-β1 protein level in blood plasma and livers of infected mice, as shown in Figures 1(a) and 1(b). However, the mRNA expression level of mouse TGF-β1 decreased significantly in all time courses after Sj infection (Figure 5(c)). These results suggested that high protein level of TGF-β1 was transcribed mainly from Sj, but not from mice. This finding was consistent with the low transcriptional level of TGF-β1 in the liver during Sj infection, as reported by Bartley et al. [35], although Bartley et al. did not test TGF-β1 from the parasite.


Tissue Transglutaminase-Regulated Transformed Growth Factor-β1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

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)

TGF-β1 is transcribed in Sj and Sj-infected mouse liver. Equal amounts of total RNA from left lobes of BALB/c mice liver with 20 ± 3 infective cercariae of Sj for 5, 6, 8, and 12 weeks were detected for TGF-β1 mRNA expression in Sj by using PCR (a) and SYBR Green-based quantitative PCR (b). Sj tubulin-α was detected as an input control. ∗P < 0.05, ∗∗P < 0.01. (c) Equal amounts of total RNA from infected mice livers at indicated time points were detected for mouse TGF-β1 mRNA expression by SYBR Green-based quantitative PCR. GAPDH was detected as an input control. ∗P < 0.05, ∗∗P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493306&req=5

fig5: TGF-β1 is transcribed in Sj and Sj-infected mouse liver. Equal amounts of total RNA from left lobes of BALB/c mice liver with 20 ± 3 infective cercariae of Sj for 5, 6, 8, and 12 weeks were detected for TGF-β1 mRNA expression in Sj by using PCR (a) and SYBR Green-based quantitative PCR (b). Sj tubulin-α was detected as an input control. ∗P < 0.05, ∗∗P < 0.01. (c) Equal amounts of total RNA from infected mice livers at indicated time points were detected for mouse TGF-β1 mRNA expression by SYBR Green-based quantitative PCR. GAPDH was detected as an input control. ∗P < 0.05, ∗∗P < 0.01.
Mentions: To gain a better understanding of the source of TGF-β1 in hepatic fibrogenesis, the transcriptional levels of TGF-β1 in mice and Sj were evaluated using RT-PCR and SYBR Green quantitative PCR. Sj-infected mouse liver cDNA was prepared as a PCR template, and the specific primer pairs shown in Figure 4(a) were also used. TGF-β1 mRNA expression level in Sj increased, especially at week 8 (Figures 5(a) and 5(b)), and this level was comparable with the TGF-β1 protein level in blood plasma and livers of infected mice, as shown in Figures 1(a) and 1(b). However, the mRNA expression level of mouse TGF-β1 decreased significantly in all time courses after Sj infection (Figure 5(c)). These results suggested that high protein level of TGF-β1 was transcribed mainly from Sj, but not from mice. This finding was consistent with the low transcriptional level of TGF-β1 in the liver during Sj infection, as reported by Bartley et al. [35], although Bartley et al. did not test TGF-β1 from the parasite.

Bottom Line: During tTG inhibition, TGF-β1 level decreased in sera and liver of infected mice.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.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.

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.

No MeSH data available.


Related in: MedlinePlus