Host serum miR-223 is a potential new biomarker for Schistosoma japonicum infection and the response to chemotherapy

Particle and Fibre Toxicology

Weiqing Pan²  Dongmei Zhang¹  Xindong Xu²  Yuanbin Zhang²  Chao Chen¹  Xue Sai¹  Xing He¹ 

[1] Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China;Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine, Shanghai 200411, China

关键词: Praziquantel;    Schistosoma japonicum;    Biomarker;    Serum miRNA;    Schistosomiasis;   

Others  :  1225301
DOI  :  10.1186/1756-3305-6-272

 received in 2013-09-02, accepted in 2013-09-17,  发布年份 2013

【 摘 要 】

Background

Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the pathogenesis and progression of various human diseases. Hence, serum miRNAs are considered to be potential biomarkers for the diagnosis of human diseases. This study examined whether several miRNAs known to be commonly deregulated in liver diseases are deregulated in the serum of hosts with hepatic schistosomiasis, and thus whether they could serve as potential markers for detection of schistosome infection and evaluation of the effectiveness of chemotherapy.

Methods

We analyzed the serum levels of six selected candidate miRNA molecules (miR-146b, miR-122, miR-223, miR-199a-5p, miR-199a-3p, miR-34a) from mice, rabbits, buffalos and humans infected with Schistosoma japonicum using qPCR. We evaluated liver pathology by determining the hydroxyproline content in liver tissues. Primary resident liver cells were isolated to quantify the expression level of deregulated miRNAs. Bioinformatics analyses were also conducted to assess the potential function of miR-223.

Results

Using a mouse model of Schistosoma japonicum infection, we found that the expression level of serum miR-223 was significantly elevated after infection, but returned to near normal levels after the treatment with praziquantel (PZQ). Importantly, the level of serum miR-223 reflected the extent of liver pathology post-infection. We validated the elevated level of the circulating miR-223 in serum samples of other host species including rabbits, buffalos and humans. In addition, our results showed that miR-223 was primarily located in the Kupffer cells, but its expression levels were significantly up-regulated in hepatocytes, hepatic stellate cells and Kupffer cells after infection. Bioinformatics analyses revealed a potential functional role of miR-223 in transcription regulator activity, transcription factor activity and DNA binding.

Conclusions

This study suggested that the circulating miR-223 could serve as a potential new biomarker for the detection of schistosome infection and the assessment of the response to chemotherapy.

【 授权许可】

   
2013 He et al.; licensee BioMed Central Ltd.

【 图 表 】

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