Molecular mechanism of Wilms tumour 1-associated protein in diabetes-related dry eye disease by mediating m6A methylation modification of lncRNA NEAT1
Background: Dry eye disease (DED) is often secondary to diabetes mellitus (DM).Purpose: This study is to explore the action of Wilms tumor 1-associated protein (WTAP) in DM-DED via lncRNA NEAT1 m6A methylation.Methods: DM-DED mouse models were treated with sh-WTAP/sh-NEAT1, followed by assessment of corneal epithelial damage/histopathological changes. HCE-2 cells were exposed to hyperosmotic conditions to establish in vitro DED models and treated with oe-NEAT1/sh-NEAT1/sh-WTAP/nigericin (an NLRP3 inflammasome inducer). Cell viability/apoptosis were evaluated by CCK-8/TUNEL. Levels of WTAP/NEAT1/inflammatory factors/NLRP3 inflammasome- and apoptosis-related markers were determined. m6A modification was examined by MeRIP-qPCR and NEAT1 stability was also detected.Results: DM-DED mice exhibited up-regulated WTAP/NEAT1 expression and severe corneal damage, whereas WTAP/NEAT1 knockdown alleviated inflammation/corneal damage. In hyperosmolarity-induced HCE-2 cells, NEAT1 aggravated inflammation and apoptosis, while NEAT1 knockdown suppressed NLRP3 inflammasome activation and ameliorated cell injury. Hyperosmolarity-induced WTAP expression increased m6A modification and NEAT1 mRNA stability. WTAP mediated m6A methylation of NEAT1 and NLRP3 inflammasome activation in DM-DED mice.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Journal of drug targeting - 32(2024), 2 vom: 09. Feb., Seite 200-212 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Chen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.02.2024 Date Revised 09.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/1061186X.2023.2300682 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366439804 |
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| 100 | 1 | |a Guo, Chen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular mechanism of Wilms tumour 1-associated protein in diabetes-related dry eye disease by mediating m6A methylation modification of lncRNA NEAT1 |
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| 520 | |a Background: Dry eye disease (DED) is often secondary to diabetes mellitus (DM).Purpose: This study is to explore the action of Wilms tumor 1-associated protein (WTAP) in DM-DED via lncRNA NEAT1 m6A methylation.Methods: DM-DED mouse models were treated with sh-WTAP/sh-NEAT1, followed by assessment of corneal epithelial damage/histopathological changes. HCE-2 cells were exposed to hyperosmotic conditions to establish in vitro DED models and treated with oe-NEAT1/sh-NEAT1/sh-WTAP/nigericin (an NLRP3 inflammasome inducer). Cell viability/apoptosis were evaluated by CCK-8/TUNEL. Levels of WTAP/NEAT1/inflammatory factors/NLRP3 inflammasome- and apoptosis-related markers were determined. m6A modification was examined by MeRIP-qPCR and NEAT1 stability was also detected.Results: DM-DED mice exhibited up-regulated WTAP/NEAT1 expression and severe corneal damage, whereas WTAP/NEAT1 knockdown alleviated inflammation/corneal damage. In hyperosmolarity-induced HCE-2 cells, NEAT1 aggravated inflammation and apoptosis, while NEAT1 knockdown suppressed NLRP3 inflammasome activation and ameliorated cell injury. Hyperosmolarity-induced WTAP expression increased m6A modification and NEAT1 mRNA stability. WTAP mediated m6A methylation of NEAT1 and NLRP3 inflammasome activation in DM-DED mice | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Diabetes mellitus | |
| 650 | 4 | |a LncRNA NEAT1 | |
| 650 | 4 | |a NLRP3 | |
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| 650 | 7 | |a NEAT1 long non-coding RNA, mouse |2 NLM | |
| 700 | 1 | |a Yu, Mingyi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jinghua |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Shaozhen |e verfasserin |4 aut | |
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