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• W2780619785 abstract "Fuchs endothelial corneal dystrophy (FECD) is a genetic and oxidative stress disorder of post-mitotic human corneal endothelial cells (HCEnCs), which normally exhibit hexagonal shape and form a compact monolayer compatible with normal corneal functioning and clear vision. FECD is associated with increased DNA damage, which in turn leads to HCEnC loss, resulting in the formation rosettes and aberrant extracellular matrix (ECM) deposition in the form of pro-fibrotic guttae. Since the mechanism of ECM deposition in FECD is currently unknown, we aimed to investigate the role of endothelial-mesenchymal transition (EMT) in FECD using a previously established cellular in vitro model that recapitulates the characteristic rosette formation, by employing menadione (MN)-induced oxidative stress. We demonstrate that MN treatment alone, or a combination of MN and TGF-β1 induces reactive oxygen species (ROS), cell death, and EMT in HCEnCs during rosette formation, resulting in upregulation of EMT- and FECD-associated markers such as Snail1, N-cadherin, ZEB1, and transforming growth factor-beta-induced (TGFβI), respectively. Additionally, FECD ex vivo specimens displayed a loss of organized junctional staining of plasma membrane-bound N-cadherin, with corresponding increase in fibronectin and Snail1 compared to ex vivo controls. Addition of N-acetylcysteine (NAC) downregulated all EMT markers and abolished rosette formation. Loss of NQO1, a metabolizing enzyme of MN, led to greater increase in intracellular ROS levels as well as a significant upregulation of Snail1, fibronectin, and N-cadherin compared to normal cells, indicating that NQO1 regulates Snail1-mediated EMT. This study provides first line evidence that MN-induced oxidative stress leads to EMT in corneal endothelial cells, and the effect of which is further potentiated when redox cycling activity of MN is enhanced by the absence of NQO1. Given that NAC inhibits Snail-mediated EMT, this may be a potential therapeutic intervention for FECD." @default.
• W2780619785 created "2018-01-05" @default.
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• W2780619785 date "2018-02-01" @default.
• W2780619785 modified "2023-10-17" @default.
• W2780619785 title "NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy" @default.
• W2780619785 cites W1512854868 @default.
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• W2780619785 cites W1556317441 @default.
• W2780619785 cites W1558909828 @default.
• W2780619785 cites W1564961043 @default.
• W2780619785 cites W1571263028 @default.
• W2780619785 cites W1760215417 @default.
• W2780619785 cites W1958735577 @default.
• W2780619785 cites W1964847767 @default.
• W2780619785 cites W1967673384 @default.
• W2780619785 cites W1972810886 @default.
• W2780619785 cites W1976022676 @default.
• W2780619785 cites W1979988883 @default.
• W2780619785 cites W1982339780 @default.
• W2780619785 cites W1984434134 @default.
• W2780619785 cites W1986969294 @default.
• W2780619785 cites W1993326322 @default.
• W2780619785 cites W1993704177 @default.
• W2780619785 cites W1995519585 @default.
• W2780619785 cites W2003431583 @default.
• W2780619785 cites W2007647018 @default.
• W2780619785 cites W2007691559 @default.
• W2780619785 cites W2024018823 @default.
• W2780619785 cites W2025647419 @default.
• W2780619785 cites W2026568179 @default.
• W2780619785 cites W2028457976 @default.
• W2780619785 cites W2030699054 @default.
• W2780619785 cites W2030808611 @default.
• W2780619785 cites W2031388684 @default.
• W2780619785 cites W2031586702 @default.
• W2780619785 cites W2032230139 @default.
• W2780619785 cites W2032942532 @default.
• W2780619785 cites W2048738817 @default.
• W2780619785 cites W2050762235 @default.
• W2780619785 cites W2052290897 @default.
• W2780619785 cites W2052644678 @default.
• W2780619785 cites W2054282870 @default.
• W2780619785 cites W2055312095 @default.
• W2780619785 cites W2061210660 @default.
• W2780619785 cites W206846325 @default.
• W2780619785 cites W2068485963 @default.
• W2780619785 cites W2075382404 @default.
• W2780619785 cites W2079678113 @default.
• W2780619785 cites W2086378628 @default.
• W2780619785 cites W2087367170 @default.
• W2780619785 cites W2091609918 @default.
• W2780619785 cites W2091726616 @default.
• W2780619785 cites W2093801720 @default.
• W2780619785 cites W2096879602 @default.
• W2780619785 cites W2107857795 @default.
• W2780619785 cites W2113163706 @default.
• W2780619785 cites W2119075662 @default.
• W2780619785 cites W2130408535 @default.
• W2780619785 cites W2134203671 @default.
• W2780619785 cites W2136032965 @default.
• W2780619785 cites W2137383541 @default.
• W2780619785 cites W2141516759 @default.
• W2780619785 cites W2148498794 @default.
• W2780619785 cites W2151316743 @default.
• W2780619785 cites W2154589460 @default.
• W2780619785 cites W2156273277 @default.
• W2780619785 cites W2161918376 @default.
• W2780619785 cites W2170331002 @default.
• W2780619785 cites W2184726787 @default.
• W2780619785 cites W2316067769 @default.
• W2780619785 cites W2317201281 @default.
• W2780619785 cites W2338036122 @default.
• W2780619785 cites W2405123385 @default.
• W2780619785 cites W2519043862 @default.
• W2780619785 cites W2533146992 @default.
• W2780619785 cites W2566910587 @default.
• W2780619785 cites W2597632520 @default.
• W2780619785 cites W2607906608 @default.
• W2780619785 cites W2737537149 @default.
• W2780619785 cites W4211224216 @default.
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• W2780619785 doi "https://doi.org/10.1016/j.freeradbiomed.2017.12.036" @default.
• W2780619785 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5815941" @default.
• W2780619785 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29294389" @default.
• W2780619785 hasPublicationYear "2018" @default.
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