miR-186-5p improves alveolar epithelial barrier function by targeting the wnt5a/ß-catenin signaling pathway in sepsis-acute lung injury.
Int Immunopharmacol
; 131: 111864, 2024 Apr 20.
Article
in En
| MEDLINE
| ID: mdl-38484663
ABSTRACT
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/ß-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/ß-catenin.RESULTS:
miR-186-5p expression was decreased, wnt5a expression was increased, and the wnt5a/ß-catenin signaling pathway was activated in mouse lung tissues and A549 cells after inflammatory stimulation. miR-186-5p overexpression resulted in wnt5a/ß-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/ß-catenin activator Licl.CONCLUSION:
Our experimental data suggest miR-186-5p targets the wnt5a/ß-catenin pathway, thereby regulating alveolar epithelial barrier function. Furthermore, both miR-186-5p and wnt5a/ß-catenin are potential therapeutic targets that could impact sepsis-ALI.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sepsis
/
MicroRNAs
/
Acute Lung Injury
Limits:
Animals
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2024
Type:
Article