Oxidative stress-mediated TXNIP loss causes RPE dysfunction

Cited 21 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorMin Ji Cho-
dc.contributor.authorSung Jin Yoon-
dc.contributor.authorWooil Kim-
dc.contributor.authorJongjin Park-
dc.contributor.authorJangwook Lee-
dc.contributor.authorJong Gil Park-
dc.contributor.authorYoung Lai Cho-
dc.contributor.authorJ H Kim-
dc.contributor.authorHyejin Jang-
dc.contributor.authorYoung-Jun Park-
dc.contributor.authorSang Hyun Lee-
dc.contributor.authorJeong Ki Min-
dc.date.accessioned2020-02-07T16:30:06Z-
dc.date.available2020-02-07T16:30:06Z-
dc.date.issued2019-
dc.identifier.issnI000-0028-
dc.identifier.uri10.1038/s12276-019-0327-yko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/19046-
dc.description.abstractThe disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood-retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.-
dc.publisherSpringer-Nature Pub Group-
dc.titleOxidative stress-mediated TXNIP loss causes RPE dysfunction-
dc.title.alternativeOxidative stress-mediated TXNIP loss causes RPE dysfunction-
dc.typeArticle-
dc.citation.titleExperimental and Molecular Medicine-
dc.citation.number10-
dc.citation.endPage121-
dc.citation.startPage121-
dc.citation.volume51-
dc.contributor.affiliatedAuthorMin Ji Cho-
dc.contributor.affiliatedAuthorSung Jin Yoon-
dc.contributor.affiliatedAuthorWooil Kim-
dc.contributor.affiliatedAuthorJongjin Park-
dc.contributor.affiliatedAuthorJangwook Lee-
dc.contributor.affiliatedAuthorJong Gil Park-
dc.contributor.affiliatedAuthorYoung Lai Cho-
dc.contributor.affiliatedAuthorHyejin Jang-
dc.contributor.affiliatedAuthorYoung-Jun Park-
dc.contributor.affiliatedAuthorSang Hyun Lee-
dc.contributor.affiliatedAuthorJeong Ki Min-
dc.contributor.alternativeName조민지-
dc.contributor.alternativeName윤성진-
dc.contributor.alternativeName김우일-
dc.contributor.alternativeName박종진-
dc.contributor.alternativeName이장욱-
dc.contributor.alternativeName박종길-
dc.contributor.alternativeName조영래-
dc.contributor.alternativeName김정훈-
dc.contributor.alternativeName장혜진-
dc.contributor.alternativeName박영준-
dc.contributor.alternativeName이상현-
dc.contributor.alternativeName민정기-
dc.identifier.bibliographicCitationExperimental and Molecular Medicine, vol. 51, no. 10, pp. 121-121-
dc.identifier.doi10.1038/s12276-019-0327-y-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.