Autophagy and keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress Ahruem Baek1, Hyewon Chung2, Dong-Eun Kim1,* 1Department of Bioscience and Biotechnology, Konkuk University, Gwangjin-gu, Seoul, Korea; 2Department of Ophthalmology, Konkuk University, School of Medicine, Gwangjin-gu, Seoul, Korea *Corresponding Author
Contribution of autophagy and regulation of related proteins to the degeneration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD) remain unknown. We report that up-regulation of keratin 8 (KRT8) as well as its phosphorylation are accompanied with autophagy and attenuated with the inhibition of autophagy in RPE cells under oxidative stress. KRT8 appears to have a dual role in RPE pathophysiology. While increased expression of KRT8 following autophagy provides a cytoprotective role in RPE, phosphorylation of KRT8 induces pathologic epithelial-mesenchymal transition (EMT) of RPE cells under oxidative stress, which is mediated by mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK). Inhibition of autophagy further promotes EMT, which can be reversed by inhibition of MAPK. Thus, regulated enhancement of autophagy with concurrent increased expression of KRT8 and the inhibition of KRT8 phosphorylation serve to inhibit oxidative stress-induced EMT of RPE cells as well as to prevent cell death, suggesting that pharmacological manipulation of KRT8 upregulation through autophagy with combined inhibition of MAPK pathway may be attractive therapeutic strategies for the treatment of AMD.
Funding This research was supported by the National Research Foundation of Korea (NRF-2017R1E1A1A01074656).
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