miR-186-5p improves alveolar epithelial barrier function by targeting the wnt5a/β-catenin signaling pathway in sepsis-acute lung injury
Copyright © 2024 Elsevier B.V. All rights reserved..
BACKGROUND: Alveolar epithelial barrier dysfunction is one of the pathological features of sepsis-acute lung injury(ALI). However, the molecular mechanisms that regulate the function of alveolar epithelial barrier remain unclear. This study aimed to determine the regulatory role of miR-186-5p in alveolar epithelial barrier function in sepsis-ALI and its underlying molecular mechanism.
METHODS: We established sepsis-ALI models in vivo and in vitro, detected the miR-186-5p and wnt5a/β-catenin expressions, and observed the functional changes of the alveolar epithelial barrier by miR-186-5p overexpression. We used rescue experiments to clarify whether miR-186-5p works through wnt5a/β-catenin.
RESULTS: miR-186-5p expression was decreased, wnt5a expression was increased, and the wnt5a/β-catenin signaling pathway was activated in mouse lung tissues and A549 cells after inflammatory stimulation. miR-186-5p overexpression resulted in wnt5a/β-catenin signaling pathway inhibition, decreased apoptosis in A549 cells, improved alveolar epithelial barrier function, reduced lung tissue injury in ALI mice, decreased IL-6 and TNF-α levels, and increased claudin4 and ZO-1 expression. Using miRNA-related database prediction and dual-luciferase reporter gene analysis, the targeting relationship between miR-186-5p and wnt5a was determined. The protective effect produced by miR-186-5p overexpression on the alveolar barrier was reversed after the application of the wnt5a/β-catenin activator Licl.
CONCLUSION: Our experimental data suggest miR-186-5p targets the wnt5a/β-catenin pathway, thereby regulating alveolar epithelial barrier function. Furthermore, both miR-186-5p and wnt5a/β-catenin are potential therapeutic targets that could impact sepsis-ALI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
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| Enthalten in: |
International immunopharmacology - 131(2024) vom: 20. Apr., Seite 111864 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Mei [VerfasserIn] |
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| Links: |
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| Themen: |
Acute lung injury |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111864 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369743547 |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Alveolar epithelial barrier dysfunction is one of the pathological features of sepsis-acute lung injury(ALI). However, the molecular mechanisms that regulate the function of alveolar epithelial barrier remain unclear. This study aimed to determine the regulatory role of miR-186-5p in alveolar epithelial barrier function in sepsis-ALI and its underlying molecular mechanism | ||
| 520 | |a METHODS: We established sepsis-ALI models in vivo and in vitro, detected the miR-186-5p and wnt5a/β-catenin expressions, and observed the functional changes of the alveolar epithelial barrier by miR-186-5p overexpression. We used rescue experiments to clarify whether miR-186-5p works through wnt5a/β-catenin | ||
| 520 | |a RESULTS: miR-186-5p expression was decreased, wnt5a expression was increased, and the wnt5a/β-catenin signaling pathway was activated in mouse lung tissues and A549 cells after inflammatory stimulation. miR-186-5p overexpression resulted in wnt5a/β-catenin signaling pathway inhibition, decreased apoptosis in A549 cells, improved alveolar epithelial barrier function, reduced lung tissue injury in ALI mice, decreased IL-6 and TNF-α levels, and increased claudin4 and ZO-1 expression. Using miRNA-related database prediction and dual-luciferase reporter gene analysis, the targeting relationship between miR-186-5p and wnt5a was determined. The protective effect produced by miR-186-5p overexpression on the alveolar barrier was reversed after the application of the wnt5a/β-catenin activator Licl | ||
| 520 | |a CONCLUSION: Our experimental data suggest miR-186-5p targets the wnt5a/β-catenin pathway, thereby regulating alveolar epithelial barrier function. Furthermore, both miR-186-5p and wnt5a/β-catenin are potential therapeutic targets that could impact sepsis-ALI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute lung injury | |
| 650 | 4 | |a Alveolar barrier | |
| 650 | 4 | |a Sepsis | |
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| 700 | 1 | |a Wu, Yanli |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xigang |e verfasserin |4 aut | |
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