A Novel miRNA From Egg-Derived Exosomes of Schistosoma japonicum Promotes Liver Fibrosis in Murine Schistosomiasis

被引:19
作者
Wang, Yiluo [1 ,2 ]
Gong, Wenci [1 ]
Zhou, Hao [1 ,2 ]
Hu, Yuan [1 ,3 ]
Wang, Lan [2 ]
Shen, Yujuan [1 ,3 ]
Yu, Guoying [2 ]
Cao, Jianping [1 ,3 ]
机构
[1] World Hlth Org Collaborating Ctr Trop Dis, Natl Hlth Commiss Peoples Republ China, Natl Inst Parasit Dis, Key Lab Parasite & Vector Biol,Chinese Ctr Trop Di, Shanghai, Peoples R China
[2] Henan Normal Univ, Coll Life Sci, State Key Lab Cell Differentiat & Regulat, Xinxiang, Peoples R China
[3] Shanghai Jiao Tong Univ, Chinese Ctr Trop Dis Res, Sch GlobalHealth, Sch Med, Shanghai, Peoples R China
关键词
Schistosoma japonicum; schistosomiasis; exosomes; microRNAs; hepatic fibrosis; TGF-beta pathway; TGF-beta RI; CROSS-SPECIES REGULATION; HEPATIC STELLATE CELLS; MICRORNAS; ACTIVATION; GROWTH; MIGRATION; RECEPTOR; PATHWAY;
D O I
10.3389/fimmu.2022.860807
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Schistosomiasis caused by Schistosoma japonicum is a serious public health problem in China. Granuloma and hepatic fibrosis are the main pathological features of schistosomiasis japonica. The role and mechanism of egg-derived exosomes of S. japonicum in liver fibrosis remain unclear. In this study, we found that egg-derived exosomes of S. japonicum carry a new type of microRNA (miRNA-33). In vitro, this novel miRNA upregulated the expression of smooth muscle actin (alpha-SMA) and collagen 1 alpha 1 (Col 1 alpha 1) in the human hepatic stellate cell (LX-2) line at both mRNA and protein levels. In vivo, this novel miRNA was upregulated in the serum of infected mice, and when injected into mice through the tail vein using miRNA agomir, alpha-SMA, Col 1 alpha 1, and Col 3 alpha 1 were upregulated in liver tissue at both mRNA and protein levels. In addition, this novel miRNA downregulated the expression of alpha-SMA and Col 1 alpha 1 in liver tissue at mRNA and protein levels in mice infected with S. japonicum and treated with miRNA antagomir. The novel miRNA-33 upregulated TGF-beta Receptor I (TGF-beta RI) at both mRNA and protein levels in LX-2 cells. Our results suggest that this novel miRNA from egg-derived exosomes of S. japonicum can promote liver fibrosis in the host in a cross-species manner, and the degree of fibrosis can be decreased by inhibiting the expression of this miRNA.
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页数:12
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