Curcumol inhibits ferritinophagy to restrain hepatocyte senescence through YAP/NCOA4 in non-alcoholic fatty liver disease.
Curcumol inhibits ferritinophagy to restrain hepatocyte senescence through YAP/NCOA4 in non-alcoholic fatty liver disease.
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姜黄素通过YAP/NCOA4抑制铁蛋白吞噬抑制非酒精性脂肪肝肝细胞衰老
DOI：
10.1111/cpr.13107
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发表时间：
2021-09
影响因子：
8.5
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Qi X;Song A;Ma M;Wang P;Zhang X;Lu C;Zhang J;Zheng S;Jin H
近年来，细胞衰老因其与非酒精性脂肪性肝病（NAFLD）的相关性而引起了研究人员的广泛兴趣。然而，细胞衰老的机制尚不清楚。本研究的目的是探讨姜黄酚对 NAFLD 肝细胞衰老的影响及其分子机制。使用LVG金色叙利亚仓鼠、C57BL/6J小鼠和人肝细胞系LO2。通过分析衰老标记 SA-β-gal、p16 和 p21、H3K9me3、γ-H2AX 和端粒酶活性来评估细胞衰老。结果表明，姜黄酚在体内和体外NAFLD模型中均能抑制肝细胞衰老，其机制可能与其调节铁蛋白自噬进而缓解铁过载有关。此外，核受体辅激活因子4（NCOA4）的过度表达削弱了姜黄酚对铁蛋白自噬介导的铁超载和细胞衰老的影响。此外，我们证明姜黄酚通过 Yes 相关蛋白（YAP）降低 NCOA4 的表达。此外，YAP 的抑制可能会削弱姜黄酚对铁过载和细胞衰老的作用。我们的结果阐明了姜黄醇通过 YAP/NCOA4 调节 NAFLD 中铁蛋白吞噬抑制肝细胞衰老的机制。这些发现为姜黄酚通过靶向 YAP/NCOA4 调节细胞衰老来治疗 NAFLD 提供了一种有前景的选择。姜黄酚通过抑制铁蛋白自噬介导的铁过载来抑制肝细胞衰老。此外，姜黄酚的这种作用与 NAFLD 模型中 YAP/NCOA4 的调节有关。
In recent years, cellular senescence has attracted a lot of interest in researchers due to its involvement in non‐alcoholic fatty liver disease (NAFLD). However, the mechanism of cellular senescence is not clear. The purpose of this study was to investigate the effect of curcumol on hepatocyte senescence in NAFLD and the molecular mechanisms implicated. LVG Golden Syrian hamsters, C57BL/6J mice and human hepatocyte cell line LO2 were used. Cellular senescence was assessed by analyses of senescence marker SA‐β‐gal, p16 and p21, H3K9me3, γ‐H2AX and telomerase activity. The results showed that curcumol could inhibit hepatocyte senescence in both in vivo and in vitro NAFLD models, and the mechanism might be related to its regulation of ferritinophagy and subsequent alleviation of iron overload. Moreover, overexpression of nuclear receptor coactivator 4 (NCOA4) weakened the effect of curcumol on ferritinophagy‐mediated iron overload and cellular senescence. Furthermore, we demonstrated that curcumol reduced the expression of NCOA4 by Yes‐associated protein (YAP). In addition, depression of YAP could impair the effect of curcumol on iron overload and cellular senescence. Our results clarified the mechanism of curcumol inhibition of hepatocyte senescence through YAP/NCOA4 regulation of ferritinophagy in NAFLD. These findings provided a promising option of curcumol to regulate cellular senescence by target YAP/NCOA4 for the treatment of NAFLD. Curcumol inhibited hepatocyte senescence by suppressing ferritinophagy‐mediated iron overload. Furthermore, this effect of curcumol is related to the regulation of YAP/NCOA4 in NAFLD models.
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影响因子：
14.9
作者：
Lin J;Countryman P;Buncher N;Kaur P;E L;Zhang Y;Gibson G;You C;Watkins SC;Piehler J;Opresko PL;Kad NM;Wang H
通讯作者：
Wang H
影响因子：
64.8
作者：
Mancias, Joseph D.;Wang, Xiaoxu;Gygi, Steven P.;Harper, J. Wade;Kimmelman, Alec C.
通讯作者：
Kimmelman, Alec C.
抑制 YAP 信号传导导致四甲基吡嗪诱导的肝星状细胞衰老
影响因子：
4.6
作者：
Jin, Huanhuan;Lian, Naqi;Zheng, Shizhong
通讯作者：
Zheng, Shizhong
DOI：
10.3390/ph11040114
发表时间：
2018-10-23
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Santana-Codina N;Mancias JD
通讯作者：
Mancias JD
影响因子：
25.7
作者：
Aravinthan, Aloysious;Scarpini, Cinzia;Alexander, Graeme
通讯作者：
Alexander, Graeme