Activation of TAF9 via Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease.
Activation of TAF9 via Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease.
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通过丹参素诱导的 HDAC1 表达上调激活 TAF9 可缓解非酒精性脂肪肝
DOI：
10.3389/fphar.2021.775528
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发表时间：
2021
影响因子：
5.6
通讯作者：
Yao J
中科院分区：
文献类型：
--
作者：
Wang R;Wang Z;Sun R;Fu R;Sun Y;Zhu M;Geng Y;Gao D;Tian X;Zhao Y;Yao J
脂肪酸β-氧化是非酒精性脂肪性肝病（NAFLD）的重要致病机制，TATA盒结合蛋白相关因子9（TAF 9）参与了脂肪酸β-氧化的调控。然而，TAF 9在NAFLD中的功能以及TAF 9的调节机制仍不清楚。在这项研究中，我们的目的是研究TAF 9参与NAFLD的信号转导机制，以及天然酚类化合物丹参素（DSS）通过HDAC 1/TAF 9通路对NAFLD的保护作用。开发了高脂饮食（HFD）诱导的NAFLD的体内模型和棕榈酸（PA）处理的AML-12细胞模型。DSS的药物治疗显著增加了NAFLD中脂肪酸β-氧化并减少了脂滴（LD）蓄积。TAF 9过表达在体内和体外对这些过程具有相同的作用。有趣的是，DSS的保护作用被TAF 9敲低显著阻断。从机制上讲，TAF 9被HDAC 1脱乙酰化，HDAC 1调节TAF 9在NAFLD期间介导脂肪酸β-氧化和LD积累的能力。总之，TAF 9是NAFLD治疗中的关键调节剂，其通过增加脂肪酸β-氧化和减少LD积累起作用，DSS通过HDAC 1/TAF 9途径提供针对NAFLD的保护。
Fatty acid β-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid β-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid β-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid β-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid β-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.
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影响因子：
5.6
作者：
Hong M;Li S;Wang N;Tan HY;Cheung F;Feng Y
通讯作者：
Feng Y
影响因子：
82.9
作者：
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Sanyal AJ
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4.2
作者：
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Park, Se Jin
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影响因子：
4.5
作者：
Fan W;Lam SM;Xin J;Yang X;Liu Z;Liu Y;Wang Y;Shui G;Huang X
通讯作者：
Huang X
影响因子：
5.4
作者：
Chen, Yuan-Cheng;Cao, Wan-Wen;Liu, Xiao-Quan
通讯作者：
Liu, Xiao-Quan