由SIRT6激活的自噬调节视网膜色素上皮细胞中Aβ诱导的炎症反应。
Autophagy activated by SIRT6 regulates Aβ induced inflammatory response in RPEs.
作者信息
Feng Yiji, Liang Jian, Zhai Yuanqi, Sun Junran, Wang Jing, She Xiangjun, Gu Qing, Liu Yang, Zhu Hong, Luo Xueting, Sun Xiaodong
机构信息
Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.
出版信息
Biochem Biophys Res Commun. 2018 Feb 19;496(4):1148-1154. doi: 10.1016/j.bbrc.2018.01.159. Epub 2018 Jan 31.
Age-associated dysfunction of retinal pigment epithelial cells (RPEs) is considered to be the initial trigger of retinal diseases such as age-related macular degeneration. Although autophagy is upregulated in RPEs during the course of aging, little is known about how autophagy is regulated and its functional role in RPEs. In this study, we found that expression of Sirtuin 6 (SIRT6) and autophagic markers are upregulated in RPEs of aged mice where subretinal deposition of amyloid-β is accumulated and in amyloid-β stimulated RPEs. In addition, gain and loss-of-function studies confirmed the positive role of SIRT6 in regulating autophagy. Interesting, inhibition of autophagy attenuates amyloid-β stimulated inflammatory response in RPEs. Collectively, our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-β induced RPE dysfunction.
视网膜色素上皮细胞（RPE）与年龄相关的功能障碍被认为是视网膜疾病如年龄相关性黄斑变性的初始触发因素。尽管在衰老过程中RPE中的自噬上调，但关于自噬如何被调节及其在RPE中的功能作用知之甚少。在本研究中，我们发现，在老年小鼠的RPE中，淀粉样β蛋白在视网膜下沉积积累，以及在淀粉样β刺激的RPE中，沉默调节蛋白6（SIRT6）和自噬标志物的表达上调。此外，功能获得和功能丧失研究证实了SIRT6在调节自噬中的积极作用。有趣的是，自噬的抑制减弱了淀粉样β刺激的RPE中的炎症反应。总的来说，我们的研究结果揭示，由SIRT6调节的自噬可能是淀粉样β诱导的RPE功能障碍的一种促炎机制。
Zotero 插件