Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
Department of Health, Research Institute for Tropical Medicine, Manila 1781, Philippines.
Int J Mol Sci. 2020 May 18;21(10):3560. doi: 10.3390/ijms21103560.
Chronic infection with or results in hepatic fibrosis of the human host. The staging of fibrosis is crucial for prognosis and to determine the need for treatment of patients with schistosomiasis. This study aimed to determine whether there is a correlation between the levels of serum exosomal micro-ribonucleic acids (miRNAs) (exomiRs) and fibrosis progression in schistosomiasis. Reference gene (RG) validation was initially carried out for the analysis of serum exomiRs expression in staging liver fibrosis caused by schistosome infection. The expression levels of liver fibrosis-associated exomiRs in serum were determined in a murine schistosomiasis model and in a cohort of Filipino schistosomiasis japonica patients ( = 104) with different liver fibrosis grades. Of twelve RG candidates validated, miR-103a-3p and miR-425-5p were determined to be the most stable genes in the murine schistosomiasis model and subjects from the schistosomiasis-endemic area, respectively. The temporal expression profiles of nine fibrosis-associated serum exomiRs, as well as their correlations with the liver pathologies, were determined in C57BL/6 mice during infection. The serum levels of three exomiRs (miR-92a-3p, miR-146a-5p and miR-532-5p) were able to distinguish subjects with fibrosis grades I-III from those with no fibrosis, but only the serum level of exosomal miR-146a-5p showed potential for distinguishing patients with mild (grades 0-I) versus severe fibrosis (grades II-III). The current data imply that serum exomiRs can be a supplementary tool for grading liver fibrosis in hepatosplenic schistosomiasis with moderate accuracy.
慢性感染 或 会导致人类宿主的肝纤维化。纤维化的分期对于预后和确定是否需要治疗血吸虫病患者至关重要。本研究旨在确定血清外泌体 micro-RNAs (miRNAs) (exomiRs) 的水平与血吸虫感染引起的纤维化进展之间是否存在相关性。首先对参考基因 (RG) 进行验证，以分析由血吸虫感染引起的肝纤维化分期的血清 exomiRs 表达。在小鼠血吸虫病模型和不同纤维化程度的菲律宾日本血吸虫病患者队列 (n = 104) 中，测定了与肝纤维化相关的血清 exomiRs 的表达水平。在十二种经验证的 RG 候选物中，miR-103a-3p 和 miR-425-5p 分别被确定为小鼠血吸虫病模型和血吸虫病流行地区的最稳定基因。在 感染期间，测定了 9 种与纤维化相关的血清 exomiRs 的时间表达谱及其与肝病理学的相关性。在 C57BL/6 小鼠中，三种 exomiRs (miR-92a-3p、miR-146a-5p 和 miR-532-5p) 的血清水平能够区分纤维化程度为 I-III 级的受试者与无纤维化的受试者，但只有外泌体 miR-146a-5p 的血清水平显示出区分轻度纤维化 (0-I 级) 和严重纤维化 (II-III 级) 的潜力。目前的数据表明，血清 exomiRs 可以作为一种辅助工具，以中等准确性对肝脾血吸虫病的肝纤维化进行分级。
