Histone Deacetylase 6 Regulates the Activation of M1 Macrophages by the Glycolytic Pathway During Acute Liver Failure

组蛋白去乙酰化酶 6 在急性肝衰竭期间通过糖酵解途径调节 M1 巨噬细胞的激活

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作者:Yao Wang #, Xun Li #, Qian Chen, Fangzhou Jiao, Chunxia Shi, Maohua Pei, Luwen Wang, Zuojiong Gong

Background

The glycolysis pathway of M1 macrophages is a key factor affecting the inflammatory response. The

Conclusion

ACY-1215 could inhibit the activation of M1 macrophages by improving the glycolytic pathway through regulating DNMT1 and DDX3X/NLRP3 signals to alleviate ALF.

Results

ALF patients and mice have significant energy metabolism disorders, accompanied by activation of M1 macrophages. After the intervention of ACY-1215, the activated M1 macrophages and cytokines levels in the mouse liver were reduced. The levels of IDH1, MDH1, and ATP were significantly increased. The expression of DDX3X increased, while the expression of NLRP3 and DNMT1 decreased. ACY-1215 could reduce the model cell apoptosis level and inflammatory response, and improve energy metabolism. It could also promote the expression of DDX3X, and inhibit the expression of NLRP3 and DNMT1.

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