日本血吸虫EV-miRNA sja-miR-2a-3p通过抑制肝星状细胞中的BCL2来限制肝纤维化
Host-parasite cross-species regulation by Schistosoma japonicum EV-miRNA sja-miR-2a-3p limits hepatic fibrosis via BCL2 suppression in hepatic stellate cells.
摘要(中文译文)
血吸虫病仍是一种重要的人兽共患寄生虫病，肝纤维化是日本血吸虫感染后慢性病理的主要表现。在血吸虫病中，肝纤维化是严重病理损伤的主要原因。然而，在血吸虫寄生虫与其宿主长期协同进化和共存的過程中，寄生虫可通过细胞外囊泡（EV）介导的跨物种通讯调控宿主肝纤维化进程。本研究鉴定出一种来源于日本血吸虫的EV衍生microRNA——sja-miR-2a-3p，其可抑制宿主的肝脏病理。通过Transwell共培养和EV分离实验，我们证实蠕虫特异性的sja-miR-2a-3p可通过EV转移至肝星状细胞（HSC）。生物信息学和双荧光素酶实验揭示，宿主BCL2（一种主要的抗凋亡基因）是sja-miR-2a-3p的直接靶标。体外实验中，sja-miR-2a-3p过表达可抑制HSC增殖和迁移，并诱导线粒体功能障碍、caspase-3/-7/-9活化及凋亡。体内实验中，向日本血吸虫感染小鼠给予sja-miR-2a-3p agomir可显著下调肝脏BCL2表达，增强HSC凋亡，减轻肉芽肿形成、胶原沉积和炎症。综上所述，我们的研究结果表明，血吸虫EV递送的sja-miR-2a-3p通过促进线粒体凋亡并在功能上抑制HSC活化来减轻肝纤维化。本研究支持将sja-miR-2a-3p作为候选抗纤维化分子。
Abstract
Schistosomiasis remains an important zoonotic parasitic disease, and hepatic fibrosis is a major cause of chronic pathology following Schistosoma japonicum infection. In schistosomiasis, hepatic fibrosis is the major cause of severe pathological damage. However, during the long-term co-evolution and coexistence between Schistosoma parasites and their hosts, the parasite can modulate the host hepatic fibrotic process through extracellular vesicle (EV)-mediated cross-species communication. In this study, we identified an EV-derived microRNA from Schistosoma japonicum, sja-miR-2a-3p, that suppresses hepatic pathology in the host. Using transwell co-culture and EV-isolation experiments, we confirmed that the helminth-specific sja-miR-2a-3p could be transferred to hepatic stellate cells (HSCs) via EVs. Bioinformatic and dual-luciferase assays revealed that host BCL2, a major anti-apoptotic gene, is a direct target of sja-miR-2a-3p. In vitro, sja-miR-2a-3p overexpression suppressed HSC proliferation and migration and induced mitochondrial dysfunction, caspase-3/-7/-9 activation, and apoptosis. In vivo, administration of sja-miR-2a-3p agomir to S. japonicum-infected mice significantly downregulated hepatic BCL2 expression, enhanced HSC apoptosis, alleviated granuloma formation, collagen deposition, and inflammation. Collectively, our findings reveal that schistosome EV-delivered sja-miR-2a-3p attenuates liver fibrosis by promoting mitochondrial apoptosis and functionally suppressing HSC activation. This study supports sja-miR-2a-3p as a candidate antifibrotic molecule.
如何引用
AMA
Bowen Dong, Danlin Zhu, Junhan Xiong, Yuanzhao Sun, Ruiting Zhang, Zhiqiang Fu, et al. Host-parasite cross-species regulation by Schistosoma japonicum EV-miRNA sja-miR-2a-3p limits hepatic fibrosis via BCL2 suppression in hepatic stellate cells.. Veterinary research. 2026; doi:10.1186/s13567-026-01794-y.
APA
Bowen Dong, Danlin Zhu, Junhan Xiong, Yuanzhao Sun, Ruiting Zhang, Zhiqiang Fu, et al (2026). Host-parasite cross-species regulation by Schistosoma japonicum EV-miRNA sja-miR-2a-3p limits hepatic fibrosis via BCL2 suppression in hepatic stellate cells.. Veterinary research. https://doi.org/10.1186/s13567-026-01794-y
GB/T 7714
Bowen Dong, Danlin Zhu, Junhan Xiong, Yuanzhao Sun, Ruiting Zhang, Zhiqiang Fu, et al. Host-parasite cross-species regulation by Schistosoma japonicum EV-miRNA sja-miR-2a-3p limits hepatic fibrosis via BCL2 suppression in hepatic stellate cells.[J]. Veterinary research, 2026 doi:10.1186/s13567-026-01794-y.
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