{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:47Z","timestamp":1787026607755,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n 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\u2019s immune responses and orchestrating the pathophysiological mechanisms. Although the exosomes secreted by\n S. japonicum<\/jats:italic>\n 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\n S. japonicum<\/jats:italic>\n secrete miRNA-30, a novel miRNA.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In vitro<\/jats:italic>\n , 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.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This novel miRNA can activate hepatic stellate cells (HSCs), the prinary effector cells of hepatic fibrosis,\n in vitro<\/jats:italic>\n , i.e., it significantly increases the fibrogenic factors\n Col1<\/jats:italic>\n (\n \u03b11<\/jats:italic>\n ),\n Col3<\/jats:italic>\n (\n \u03b11<\/jats:italic>\n ), and\n \u03b1-SMA<\/jats:italic>\n at both mRNA and protein levels. In addition, miRNA-30 may activate HSCs by targeting the host RORA gene. In addition,\n in vivo<\/jats:italic>\n 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\n Col1<\/jats:italic>\n (\n \u03b11<\/jats:italic>\n ),\n Col3<\/jats:italic>\n (\n \u03b11<\/jats:italic>\n ), and\n \u03b1<\/jats:italic>\n -SMA at both the transcriptomic and proteomic scales. This overexpression was coupled with a pronounced augmentation in the hepatic hydroxyproline content. Conversely, the\n in vivo<\/jats:italic>\n silencing of miRNA-30 in infected mice induced a considerable reduction in the size of hepatic granulomas and areas of collagen deposition. Hence,\n in vivo<\/jats:italic>\n , modulation of miRNA-30 expression may play a pivotal role in ameliorating the severity of hepatic fibrosis in mice afflicted with\n S. japonica<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1425384","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:57:25Z","timestamp":1722301045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Induction of hepatic fibrosis in mice with schistosomiasis by extracellular microRNA-30 derived from Schistosoma japonicum 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