Autophagy activated by SIRT6 regulates Aβ induced inflammatory response in RPEs

被引：18

作者：

Feng, Yiji ^{[1
]}

Liang, Jian ^{[1
,2
]}

Zhai, Yuanqi ^{[1
,3
]}

Sun, Junran ^{[1
]}

Wang, Jing ^{[1
]}

She, Xiangjun ^{[1
]}

Gu, Qing ^{[2
]}

Liu, Yang ^{[1
,2
]}

Zhu, Hong ^{[1
,2
,3
]}

Luo, Xueting ^{[1
,2
]}

Sun, Xiaodong ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol,Shanghai Gen Hosp, Shanghai, Peoples R China

[2] Shanghai Key Lab Fundus Dis, Shanghai, Peoples R China

[3] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 496卷 / 04期

基金：

中国国家自然科学基金;

关键词：

RPE cells; A beta; Inflammation; SIRT6; Autophagy; MACULAR DEGENERATION; AMYLOID-BETA; MECHANISMS; DRUSEN; DISEASE;

D O I：

10.1016/j.bbrc.2018.01.159

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta is accumulated and in amyloid-beta 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-beta stimulated inflammatory response in RPEs. Collectively, our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-beta induced RPE dysfunction. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：1148 / 1154

页数：7

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