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<p><i>MST1</i> and <i>MST2</i> (<i>MST1/2</i>) are core kinases of the Hippo/YAP signaling pathway in mammals and play key roles in various liver diseases. Deep molecular profiling has shown that the Hippo/YAP pathway interacts synergistically with TGF-β<sub>1</sub>/Smad2 signaling. Salvianolic acid B (SAB) is an ingredient extracted from <i>Salvia miltiorrhiza</i> that can be used to treat liver diseases. Previous studies have confirmed that SAB hold commendable efficacy against liver injury by inhibition of inflammatory response and Smad2C/2L phosphorylation. However, scientific evidence involving how mutations in the Hippo/YAP pathway are related to the hepatoprotective function of SAB in <i>MST1/2</i> double knockout (<i>MST1/2</i> DKO) mice remains vague. Nowadays, the <i>MST1</i><sup><i>–/–</i></sup><i> MST2</i><sup><i>fl/fl</i></sup><i> Alb-Cre</i> mice were generated to establish a CCl<sub>4</sub>-induced liver injury model to investigate the potential effects of <i>MST1/2</i> gene knockout on inflammatory reactions and pSmad2C/pSmad2L signal transduction with the intervention of SAB. As it turns out, genotype identification and western blot assays confirmed that we have successfully obtained <i>MST1</i><sup><i>–/–</i></sup><i> MST2</i><sup><i>fl/fl</i></sup><i> Alb-Cre</i> mice. General observation, HE staining, and biochemical assays promulgated that genetic deletion of <i>MST1/2</i> could diminish SAB’s hepatoprotective effect on liver injury by promoting the phosphorylation of smad2C/2L and boosting the expression of the inflammatory factors IL- 6 and TNF-α. In summary, these results suggest that <i>MST1/2</i> play a key role in mediating SAB’s effects on liver injury.</p>

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MST1/2 DKO abates salvianolic acid B’s therapeutic effect on CCl4-induced liver injury mice

  • 期刊论文

  • 发表日期：

    2025年4月12日

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  • Yanyan Xu,
  • Yu Zhang,
  • Mengru Yang,
  • Changfeng Xue,
  • Yuqi Dang,
  • Yan Yang,
  • YongfangGong

摘要

MST1 and MST2 (MST1/2) are core kinases of the Hippo/YAP signaling pathway in mammals and play key roles in various liver diseases. Deep molecular profiling has shown that the Hippo/YAP pathway interacts synergistically with TGF-β1/Smad2 signaling. Salvianolic acid B (SAB) is an ingredient extracted from Salvia miltiorrhiza that can be used to treat liver diseases. Previous studies have confirmed that SAB hold commendable efficacy against liver injury by inhibition of inflammatory response and Smad2C/2L phosphorylation. However, scientific evidence involving how mutations in the Hippo/YAP pathway are related to the hepatoprotective function of SAB in MST1/2 double knockout (MST1/2 DKO) mice remains vague. Nowadays, the MST1–/– MST2fl/fl Alb-Cre mice were generated to establish a CCl4-induced liver injury model to investigate the potential effects of MST1/2 gene knockout on inflammatory reactions and pSmad2C/pSmad2L signal transduction with the intervention of SAB. As it turns out, genotype identification and western blot assays confirmed that we have successfully obtained MST1–/– MST2fl/fl Alb-Cre mice. General observation, HE staining, and biochemical assays promulgated that genetic deletion of MST1/2 could diminish SAB’s hepatoprotective effect on liver injury by promoting the phosphorylation of smad2C/2L and boosting the expression of the inflammatory factors IL- 6 and TNF-α. In summary, these results suggest that MST1/2 play a key role in mediating SAB’s effects on liver injury.