MicroRNA-181b promotes schistosomiasis-induced hepatic fibrosis by targeting Smad7

Abstract

Schistosomiasis is a common parasitic disease. Hepatosplenic schistosomiasis, caused by Schistosoma japonicum and Schistosoma mansoni, involves pathological changes, including worm egg-induced hepatic granuloma and fibrosis, which can markedly affect the liver's physiological functions. Although the drug praziquantel (PZQ) is used to treat schistosomiasis, drugs against schistosomiasis-induced liver fibrosis are rare in the clinical setting. Therefore, developing effective strategies to prevent and treat schistosomiasis-induced liver fibrosis is crucial. Previous studies have shown that miRNAs are involved in various liver diseases. In this study, we found a gradual increase in miR-181b expression in the murine liver as S. japonicum infection progressed, while the expression of Smad7 decreased. Down-regulating miR-181b significantly alleviated S. japonicum-induced hepatic granuloma and liver fibrosis. In vitro experiments showed that treatment with TGF-β1 upregulated miR-181b levels in the hepatic stellate cell (HSC) line LX2 in a concentration- and time-dependent manner. Downregulation of miR-181b significantly decreased collagen type I alpha 1 chain (COL1A1) expression in TGF-β1-stimulated LX2 cells. These findings indicate that miR-181b promotes HSC activation by down-regulating Smad7 expression, activating the TGF-β1/Smad signaling pathway, and leading to excess collagen expression and deposition. Our findings suggest that miR-181b might be a potentially novel therapeutic target for schistosomiasis-induced liver fibrosis.

Keywords: Liver fibrosis; MiR-181b; Schistosomiasis; Smad7.