Molecular biology reports · 2026
Antifibrotic activity of Schistosoma japonicum-derived sja-miR-2a-3p in carbon tetrachloride-induced liver fibrosis.
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Zhong Haoran, Dong Bowen, Li Danting, Zhu Danlin, Zhang Ruiting, Lu Ke, Li Hao, Fu Zhiqiang, Jin Yamei
Аннотация
BACKGROUND: Liver fibrosis is a common consequence of chronic liver injury and is driven largely by persistent activation of hepatic stellate cells and excessive extracellular matrix deposition. We previously identified Schistosoma japonicum-derived sja-miR-2a-3p as a parasite-derived microRNA with antifibrotic activity in schistosomiasis-associated liver fibrosis. Whether this cross-species regulatory molecule also modulates fibrogenesis beyond the context of schistosome infection remains unclear.
METHODS AND RESULTS: We investigated the effects of sja-miR-2a-3p in a carbon tetrachloride-induced mouse model of liver fibrosis. Mice received systemic administration of sja-miR-2a-3p agomir during CCL₄-induced fibrogenesis, followed by assessment of histological liver injury, fibrosis, inflammation, HSC activation, HSC-associated apoptotic activity, and transcriptomic alterations. sja-miR-2a-3p agomir administration increased sja-miR-2a-3p abundance in serum and liver tissues and markedly attenuated CCL₄-induced hepatic injury and fibrosis, as evidenced by reduced liver weight index, Ishak fibrosis scores, collagen deposition, and hepatic hydroxyproline content. sja-miR-2a-3p treatment also suppressed HSC activation and extracellular matrix production, with decreased expression of α-SMA, Col1α1, Col3α1, and TGF-β. Moreover, enhanced cleaved caspase-3 signals were observed in desmin-positive HSCs, consistent with increased apoptotic activity in activated HSCs. Hepatic expression of the inflammatory mediators TNF-α, IL-1β, and IL-6 was also reduced. Whole-liver transcriptomic analysis further showed treatment-associated downregulation of extracellular matrix-, cytokine-, chemokine-, NF-κB-, IL-17-, and TNF-related pathways.
CONCLUSIONS: sja-miR-2a-3p attenuates CCL₄-induced liver fibrosis in mice, accompanied by reduced HSC activation and extracellular matrix accumulation, enhanced HSC-associated apoptotic activity, and attenuation of inflammatory signaling. These findings extend the biological activity of sja-miR-2a-3p from schistosomiasis-associated fibrosis to a chemically induced fibrosis model and support further investigation of helminth-derived regulatory miRNAs as modulators of host fibrotic responses.
METHODS AND RESULTS: We investigated the effects of sja-miR-2a-3p in a carbon tetrachloride-induced mouse model of liver fibrosis. Mice received systemic administration of sja-miR-2a-3p agomir during CCL₄-induced fibrogenesis, followed by assessment of histological liver injury, fibrosis, inflammation, HSC activation, HSC-associated apoptotic activity, and transcriptomic alterations. sja-miR-2a-3p agomir administration increased sja-miR-2a-3p abundance in serum and liver tissues and markedly attenuated CCL₄-induced hepatic injury and fibrosis, as evidenced by reduced liver weight index, Ishak fibrosis scores, collagen deposition, and hepatic hydroxyproline content. sja-miR-2a-3p treatment also suppressed HSC activation and extracellular matrix production, with decreased expression of α-SMA, Col1α1, Col3α1, and TGF-β. Moreover, enhanced cleaved caspase-3 signals were observed in desmin-positive HSCs, consistent with increased apoptotic activity in activated HSCs. Hepatic expression of the inflammatory mediators TNF-α, IL-1β, and IL-6 was also reduced. Whole-liver transcriptomic analysis further showed treatment-associated downregulation of extracellular matrix-, cytokine-, chemokine-, NF-κB-, IL-17-, and TNF-related pathways.
CONCLUSIONS: sja-miR-2a-3p attenuates CCL₄-induced liver fibrosis in mice, accompanied by reduced HSC activation and extracellular matrix accumulation, enhanced HSC-associated apoptotic activity, and attenuation of inflammatory signaling. These findings extend the biological activity of sja-miR-2a-3p from schistosomiasis-associated fibrosis to a chemically induced fibrosis model and support further investigation of helminth-derived regulatory miRNAs as modulators of host fibrotic responses.