Autophagy activated by SIRT6 regulates Aβ induced inflammatory response in RPEs

Yiji Feng; Jian Liang; Yuanqi Zhai; Junran Sun; Jing Wang; Xiangjun She; Qing Gu; Yang Liu; Hong Zhu; Xueting Luo; Xiaodong Sun

doi:10.1016/j.bbrc.2018.01.159

Autophagy activated by SIRT6 regulates Aβ induced inflammatory response in RPEs

Biochem Biophys Res Commun. 2018 Feb 19;496(4):1148-1154. doi: 10.1016/j.bbrc.2018.01.159. Epub 2018 Jan 31.

Authors

Yiji Feng¹, Jian Liang², Yuanqi Zhai³, Junran Sun¹, Jing Wang¹, Xiangjun She¹, Qing Gu⁴, Yang Liu², Hong Zhu⁵, Xueting Luo⁶, Xiaodong Sun⁷

Affiliations

¹ Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² 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.
³ Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
⁴ Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.
⁵ 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; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
⁶ 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. Electronic address: xtluo@sjtu.edu.cn.
⁷ 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; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China. Electronic address: xdsun@sjtu.edu.cn.

PMID: 29402409
DOI: 10.1016/j.bbrc.2018.01.159

Abstract

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.

Keywords: Autophagy; Aβ; Inflammation; RPE cells; SIRT6.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / immunology*
Animals
Autophagy / drug effects
Autophagy / immunology*
Cells, Cultured
Epithelial Cells / drug effects
Epithelial Cells / immunology*
Epithelial Cells / pathology
Gene Expression Regulation / drug effects
Gene Expression Regulation / immunology
Inflammation Mediators / immunology*
Mice
Mice, Inbred C57BL
Retinal Pigment Epithelium / drug effects
Retinal Pigment Epithelium / immunology*
Retinal Pigment Epithelium / pathology
Retinitis / chemically induced
Retinitis / immunology*
Retinitis / pathology
Sirtuins / immunology*

Substances

Amyloid beta-Peptides
Inflammation Mediators
Sirt6 protein, mouse
Sirtuins