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组织转谷氨酰胺酶调节的寄生虫转化生长因子-β1将日本血吸虫感染与肝纤维化联系起来。

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

作者信息

Tang Juanjuan, Zhu Xunmin, Zhao Jingjing, Fung Mingchiu, Li Yinyan, Gao Zhiyan, Yan Suikai, Li Xiaomin, Ji Xiaofang, Su Fang, Li Zi

机构信息

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

Morphology Department, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China.

出版信息

Mediators Inflamm. 2015;2015:659378. doi: 10.1155/2015/659378. Epub 2015 Jun 23.

DOI:10.1155/2015/659378
PMID:26199461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4493306/
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.

摘要

转化生长因子（TGF-β1）是肝纤维化最强的诱导因子之一，但其与血吸虫性肝纤维化的关系仍存在争议。组织转谷氨酰胺酶（tTG）是控制TGF-β1成熟的主要酶，并在血吸虫感染所致的肝纤维化中发挥作用。在此，我们旨在探究tTG与TGF-β1之间的一致性、TGF-β1的来源及其与血吸虫感染后肝纤维化的相关性。在肝纤维化诱导后的第6周和第8周，TGF-β1表达上调。在抑制tTG期间，感染小鼠血清和肝脏中的TGF-β1水平降低。TGF-β1在含有血吸虫成虫和虫卵的肝脏中呈阳性染色。在血吸虫成虫切片、可溶性虫卵抗原、血吸虫成虫抗原以及成虫培养基中也检测到了TGF-β1。以成虫为模板，通过RT-PCR和RACE-PCR扩增TGF-β1成熟肽cDNA序列及其延伸序列，并进行序列分析，上传至NCBI基因库（编号GQ338152.1）。血吸虫虫卵中的TGF-β1转录本高于成虫。在血吸虫感染的肝脏中，来源于血吸虫而非小鼠肝脏的TGF-β1转录水平与肝纤维化程度相关。本研究为tTG调控TGF-β1提供了证据，并阐明了靶向tTG治疗血吸虫感染所致纤维化的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/555ec24680fe/MI2015-659378.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/aa19b09aa078/MI2015-659378.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/551233a8d813/MI2015-659378.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/394c79204e83/MI2015-659378.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/69b4bae66fb5/MI2015-659378.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/555ec24680fe/MI2015-659378.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/aa19b09aa078/MI2015-659378.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/551233a8d813/MI2015-659378.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/394c79204e83/MI2015-659378.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/69b4bae66fb5/MI2015-659378.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a3/4493306/555ec24680fe/MI2015-659378.005.jpg

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