PDF(Pubmed)
Abstract：
UNASSIGNED: Schistosomiasis is a zoonotic parasitic disorder induced by the infestation of schistosomes, a genus of trematodes. MicroRNAs (miRNAs) in egg-derived exosomes are crucial for modulating the host\'s immune responses and orchestrating the pathophysiological mechanisms. Although the exosomes secreted by S. japonicum contain abundant miRNAs, the specific roles of these miRNAs in the pathogenesis of schistosomiasis-induced hepatic fibrosis are yet to be comprehensively elucidated. The egg exosomes of S. japonicum secrete miRNA-30, a novel miRNA.
UNASSIGNED: In vitro, the effect of miRNA-30 was evaluated by transfecting HSCs with miRNA mimics. The target gene biosignature for miRNA-30 was predicted using the miRDB software. The effect of miRNA-30 in hepatic fibrosis was evaluated by either elevating its expression in healthy mice or by inhibiting its activity in infected mice by administration of recombinant adeno-associated virus serotype eight vectors expressing miRNA-30 or miRNA sponges.
UNASSIGNED: This novel miRNA can activate hepatic stellate cells (HSCs), the prinary effector cells of hepatic fibrosis, in vitro, i.e., it significantly increases the fibrogenic factors Col1(α1), Col3(α1), and α-SMA at both mRNA and protein levels. In addition, miRNA-30 may activate HSCs by targeting the host RORA gene. In addition, in vivo experiments were conducted by administering a recombinant adeno-associated viral vector to modulate the expression levels of miRNA-30. The overexpression of miRNA-30 in healthy mice significantly elevated the expression of Col1(α1), Col3(α1), and α-SMA at both the transcriptomic and proteomic scales. This overexpression was coupled with a pronounced augmentation in the hepatic hydroxyproline content. Conversely, the in vivo silencing of miRNA-30 in infected mice induced a considerable reduction in the size of hepatic granulomas and areas of collagen deposition. Hence, in vivo, modulation of miRNA-30 expression may play a pivotal role in ameliorating the severity of hepatic fibrosis in mice afflicted with S. japonica.
UNASSIGNED: The study results suggest that miRNA-30 may augment schistosomiasis-induced hepatic fibrosis through a probable interaction with the host RORA. Our study may improve the current theoretical framework regarding cross-species regulation by miRNAs of hepatic fibrosis in schistosomiasis.
UNASSIGNED: In vitro, the effect of miRNA-30 was evaluated by transfecting HSCs with miRNA mimics. The target gene biosignature for miRNA-30 was predicted using the miRDB software. The effect of miRNA-30 in hepatic fibrosis was evaluated by either elevating its expression in healthy mice or by inhibiting its activity in infected mice by administration of recombinant adeno-associated virus serotype eight vectors expressing miRNA-30 or miRNA sponges.
UNASSIGNED: This novel miRNA can activate hepatic stellate cells (HSCs), the prinary effector cells of hepatic fibrosis, in vitro, i.e., it significantly increases the fibrogenic factors Col1(α1), Col3(α1), and α-SMA at both mRNA and protein levels. In addition, miRNA-30 may activate HSCs by targeting the host RORA gene. In addition, in vivo experiments were conducted by administering a recombinant adeno-associated viral vector to modulate the expression levels of miRNA-30. The overexpression of miRNA-30 in healthy mice significantly elevated the expression of Col1(α1), Col3(α1), and α-SMA at both the transcriptomic and proteomic scales. This overexpression was coupled with a pronounced augmentation in the hepatic hydroxyproline content. Conversely, the in vivo silencing of miRNA-30 in infected mice induced a considerable reduction in the size of hepatic granulomas and areas of collagen deposition. Hence, in vivo, modulation of miRNA-30 expression may play a pivotal role in ameliorating the severity of hepatic fibrosis in mice afflicted with S. japonica.
UNASSIGNED: The study results suggest that miRNA-30 may augment schistosomiasis-induced hepatic fibrosis through a probable interaction with the host RORA. Our study may improve the current theoretical framework regarding cross-species regulation by miRNAs of hepatic fibrosis in schistosomiasis.
摘要：
■血吸虫病是由血吸虫侵染引起的人畜共患寄生虫病，吸虫的一个属。卵源外泌体中的microRNAs(miRNA)对于调节宿主的免疫反应和协调病理生理机制至关重要。尽管日本血吸虫分泌的外泌体含有丰富的miRNAs,这些miRNAs在血吸虫病肝纤维化发病机制中的具体作用尚待全面阐明。日本血吸虫卵外泌体分泌miRNA-30，一种新的miRNA。
■体外，通过用miRNA模拟物转染HSC来评估miRNA-30的效果。使用miRDB软件预测miRNA-30的靶基因生物特征。通过提高其在健康小鼠中的表达或通过施用表达miRNA-30或miRNA海绵的重组腺相关病毒血清型8载体抑制其在感染小鼠中的活性来评估miRNA-30在肝纤维化中的作用。
■这种新的miRNA可以激活肝星状细胞（HSC），肝纤维化的效应细胞，在体外，即，它显著增加纤维原因子Col1（α1），Col3(α1),和α-SMA在mRNA和蛋白质水平。此外,miRNA-30可能通过靶向宿主RORA基因激活HSC。此外,通过施用重组腺相关病毒载体以调节miRNA-30的表达水平进行体内实验。miRNA-30在健康小鼠中的过表达显著升高了Col1(α1)的表达,Col3(α1),和α-SMA在转录组和蛋白质组尺度上。这种过表达与肝羟脯氨酸含量的显着增加有关。相反，miRNA-30在感染小鼠体内的沉默导致肝肉芽肿的大小和胶原沉积的面积显著减少。因此，在体内，miRNA-30表达的调节可能在改善日本血吸虫小鼠肝纤维化的严重程度中起关键作用。
■研究结果表明，miRNA-30可能通过与宿主RORA的相互作用来增强血吸虫病诱导的肝纤维化。我们的研究可能会改善目前关于血吸虫病肝纤维化miRNA跨物种调控的理论框架。
■体外，通过用miRNA模拟物转染HSC来评估miRNA-30的效果。使用miRDB软件预测miRNA-30的靶基因生物特征。通过提高其在健康小鼠中的表达或通过施用表达miRNA-30或miRNA海绵的重组腺相关病毒血清型8载体抑制其在感染小鼠中的活性来评估miRNA-30在肝纤维化中的作用。
■这种新的miRNA可以激活肝星状细胞（HSC），肝纤维化的效应细胞，在体外，即，它显著增加纤维原因子Col1（α1），Col3(α1),和α-SMA在mRNA和蛋白质水平。此外,miRNA-30可能通过靶向宿主RORA基因激活HSC。此外,通过施用重组腺相关病毒载体以调节miRNA-30的表达水平进行体内实验。miRNA-30在健康小鼠中的过表达显著升高了Col1(α1)的表达,Col3(α1),和α-SMA在转录组和蛋白质组尺度上。这种过表达与肝羟脯氨酸含量的显着增加有关。相反，miRNA-30在感染小鼠体内的沉默导致肝肉芽肿的大小和胶原沉积的面积显著减少。因此，在体内，miRNA-30表达的调节可能在改善日本血吸虫小鼠肝纤维化的严重程度中起关键作用。
■研究结果表明，miRNA-30可能通过与宿主RORA的相互作用来增强血吸虫病诱导的肝纤维化。我们的研究可能会改善目前关于血吸虫病肝纤维化miRNA跨物种调控的理论框架。
