Autophagy and KRT8/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress

Baek, Ahruem; Yoon, Seok-Nam; Kim, Jean; Baek, Yu Mi; Park, Hanna; Lim, Daehan; Chung, Hyewon; Kim, Dong-Eun

doi:10.1080/15548627.2016.1256932

Cited by 59 publications

(48 citation statements)

References 65 publications

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“…Moreover, knockdown the expression or alteration of the critical phosphorylation site (Ser74) of KRT8 induced autophagy impairment, through affecting the fusion of autophagosomes and lysosomes. These results were inconsistent with the recent studies, in which phosphorylated KRT8 is always in parallel with the total KRT8 expression, and the latter facilitates the autophagic process and plays a protective role in RPE cells under oxidative stress . As demonstrated by previous reports, phosphorylation of IFs can modulate their interaction with IF‐related proteins, such as adaptor protein 14‐3‐3 .…”

Section: Discussioncontrasting

confidence: 80%

KRT8 phosphorylation regulates the epithelial‐mesenchymal transition in retinal pigment epithelial cells through autophagy modulation

Miao

Yin

et al. 2020

J Cellular Molecular Medi

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Proliferative vitreoretinopathy (PVR) is a severe ocular disease which results in complex retinal detachment and irreversible vision loss. The epithelial‐mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is considered to be critical in the pathogenesis of PVR. In this study, we focused on the potential impact of keratin 8 (KRT8) phosphorylation and autophagy on TGF‐β2–induced EMT of RPE cells and explored the relationship between them. Using immunofluorescence and Western blot analysis, the co‐localization of KRT8 and autophagy marker, as well as the abundance of phosphorylated KRT8 (p‐KRT8) expression, was observed within subretinal and epiretinal membranes from PVR patients. Moreover, during TGF‐β2–induced EMT process, we found that p‐KRT8 was enhanced in RPE cells, which accompanied by an increase in autophagic flux. Inhibition of autophagy with pharmacological inhibitors or specific siRNAs was associated with a reduction in cell migration and the synthesis of several EMT markers. In the meantime, we demonstrated that p‐KRT8 was correlated with the autophagy progression during the EMT of RPE cells. Knockdown the expression or mutagenesis of the critical phosphorylated site of KRT8 would induce autophagy impairment, through affecting the fusion of autophagosomes and lysosomes. Therefore, this study may provide a new insight into the pathogenesis of PVR and suggests the potential therapeutic value of p‐KRT8 in the prevention and treatment of PVR.

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Section: Discussioncontrasting

confidence: 80%

KRT8 phosphorylation regulates the epithelial‐mesenchymal transition in retinal pigment epithelial cells through autophagy modulation

Miao

Yin

et al. 2020

J Cellular Molecular Medi

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“…It has also been demonstrated that KRT8 is increased in retinal pigment epithelium by oxidative stress, suggesting that its increase may be a potential cytoprotective mechanism against reactive oxygen species (ROS). 54 Considering that KRT8 was mainly up-regulated under abnormal or unhealthy conditions based on previous studies and our results, it is believed that up-regulation of Krt8 in response to chronic alcohol exposure may protect the hippocampus from oxidative stress triggered by alcohol. In addition, Vim was increased by chronic alcohol exposure in our study.…”

Section: Discussionsupporting

confidence: 57%

Gene expression profiling in the hippocampus of adolescent rats after chronic alcohol administration

Choi

Han

Chai

et al. 2019

Basic Clin Pharma Tox

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In South Korea, the average age of onset of alcohol drinking is 13.3 years and half of adolescents drink alcohol more than once a month; 8.45% of the Korean adolescent population become future high‐risk alcohol drinkers. Chronic alcohol abuse causes physical and psychiatric health problems such as alcohol addiction, liver disease, stroke and cognitive impairments. This study aimed to investigate the effect of alcohol on gene expression and their function in the hippocampus of adolescent rats. After chronic alcohol administration in male (control, n = 6; alcohol, n = 6) Sprague‐Dawley rats for 6 weeks, we analysed up‐ or down‐regulated genes using RNA‐sequencing technology. We found 83 genes more than 1.5‐fold up‐ or down‐regulated in the alcohol‐treated group. Among them, genes (Dnai1, Cfap206 and Dnah1) associated with cilium movement were up‐regulated in the alcohol‐treated group. Mlf1, related to cell cycle arrest, was also up‐regulated in the alcohol‐treated group. On the other hand, genes (Smad3 and Plk5) involved in negative regulation of cell proliferation were down‐regulated in the hippocampus by chronic alcohol administration. In addition, expression levels of genes associated with oxidative stress (Krt8 and Car3) and migration (Vim) were changed by chronic alcohol administration. These results pave a path for a better understanding of the neuromolecular mechanisms mediated by chronic alcohol exposure in the hippocampus of adolescents and negative pathology due to chronic alcohol abuse.

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“…Knockdown of KRT8 in mice resulted in a reduced litter size and in the death of the pups at birth (Baribault, Price, Miyai, & Oshima, ). Besides, Baek et al () demonstrated that short‐term exposure to oxidative stress does not trigger cell death. Instead, triggers autophagy, upregulation of KRT8 and its phosphorylation to prevent apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Effect of BMP15 and/or AMH during in vitro maturation of oocytes from involuntarily culled dairy cows

Velásquez

Mellisho

Castro

et al. 2018

Molecular Reproduction Devel

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The high metabolic activity to which the dairy cattle are exposed to maintain milk production altered steroid metabolism that affects reproductive physiology and reduce oocyte competence. Our aims were (a) to characterize the competence of immature oocytes collected from dairy cattle based on the expression of genes in cumulus cells (CCs) and (b) to improve oocyte competence to support preimplantation embryo development by the supplementation of maturation medium with bone morphogenetic protein 15 (BMP15) and/or anti‐mullerian hormone (AMH). Oocyte donors were identified at the moment of ovary collection and grouped by involuntarily culled dairy cows (Holstein breed) or beef cattle. The embryo development speed to blastocyst of the cull dairy cattle versus beef cattle (control group) was lower. Besides, <10% of oocytes (with CC biopsies) derived from dairy cattle were able to develop to the blastocyst stage. In addition, a higher level of expression and a positive correlation were observed in the expression of most of the genes evaluated (LUM, KRT18, KRT8, CLIC3, BMPR1B, and SLC38A3) in the cumulus–oocyte complexes that produced blastocysts versus those which did not develop correctly (arrested development). Further, use of BMP15 in the maturation of oocytes from dairy cattle seems to increase competence, modulating the expression of OCT4, SOX2, CDX2, GATA6, and TP1 in resulting blastocysts.

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Autophagy and KRT8/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress

Cited by 59 publications

References 65 publications

KRT8 phosphorylation regulates the epithelial‐mesenchymal transition in retinal pigment epithelial cells through autophagy modulation

KRT8 phosphorylation regulates the epithelial‐mesenchymal transition in retinal pigment epithelial cells through autophagy modulation

Gene expression profiling in the hippocampus of adolescent rats after chronic alcohol administration

Effect of BMP15 and/or AMH during in vitro maturation of oocytes from involuntarily culled dairy cows

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