Sja-Let-7 Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in a Mouse Model via Col1α2
Haoran Zhong,
Bowen Dong,
Danlin Zhu,
Hao Li,
Ke Lu,
Zhiqiang Fu,
Jinming Liu,
Yamei Jin
Affiliations
Haoran Zhong
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Bowen Dong
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Danlin Zhu
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Hao Li
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Ke Lu
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Zhiqiang Fu
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Jinming Liu
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Yamei Jin
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL4)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the α2 chain of collagen type 1 (Col1α2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1α2 and the TGF-β/Smad signaling pathway.
