Abstract
Liver fibrosis, a common pathological process in chronic liver diseases, is characterized by excessive accumulation of extracellular matrix proteins and considered as a wound healing response to chronic liver injury. Hepatic stellate cell (HSC) activation plays a key role in liver fibrosis development. Previous studies showed that sulforaphane (SFN) has wide protective effects against tissue injury and inflammation. Accumulating evidence has shown that microRNAs play important roles in the development of hepatic fibrosis, some of which have been identified as potential therapeutic targets. This study was conducted to explore the role of SFN in the suppression of HSC activation. Quantitative real-time PCR showed that HSC miR-423-5p levels were up-regulated during HSC activation and down-regulated after SFN administration. Further, transfection of a miR-423-5p mimic demonstrated that inhibition of HSC activation by SFN required down-regulation of miR-423-5p. We showed that suppressor of fused is the direct target of miR-423-5p. SFN may play a role in inhibiting hepatic fibrosis by downregulating miRNA-423-5p. MiRNA-423-5p may be useful as a therapeutic target for treating hepatic fibrosis.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China [Grant number 81704016] and Natural Science Foundation of Guangdong Province [Grant number 2017A030313687].
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P.J. designed the research. F.M-H and L.J-W performed experiments, analyzed the data, and wrote the paper. H.S-Q and S.H-T performed the illustrations of the data. All authors have read and approved the final manuscript.
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Feng, MH., Li, JW., Sun, HT. et al. Sulforaphane inhibits the activation of hepatic stellate cell by miRNA-423-5p targeting suppressor of fused. Human Cell 32, 403–410 (2019). https://doi.org/10.1007/s13577-019-00264-2
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DOI: https://doi.org/10.1007/s13577-019-00264-2