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Updated: Nov 22, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
MicroRNA-144-3p enhances LPS induced septic acute lung injury in mice through downregulating Caveolin-2
Ruiming Xu1, Zhengyi Shao1, Qiumei Cao1
1Emergency Department, Beijing Tongren Hospital (South District), Beijing 100176, PR China.
Objective:
The emphasis of this study focused on the possible implication and the mechanism of miR-144-3p in septic acute lung injury (ALI) condition.
Methods:
Mice were pre-injected with miR-144-3p agomir, miR-144-3p antagomir, sh-Caveolin-2 or PBS before 10 mg/kg LPS induced sepsis model establishment. The ratio of wet weight of lung tissues and body weight (W/W) was calculated. The pathological changes on lung tissues were observed by H&E staining. Secretions of inflammatory cytokines (TNF-α, IL-1β and IL-6) in both mouse serum and lung tissues were determined by ELISA. Cell apoptosis and cell morphology were measured by TUNEL staining and H&E staining. The expressions of miR-144-3p, Caveolin-2, apoptotic related proteins and JAK/STAT pathway related proteins were measured by qRT-PCR or/and Western blot. Dual luciferase reporter assay was applied to detect the binding of miR-144-3p with Caveolin-2.
Results:
LPS resulted in increased W/W, disrupted lung tissue, enhanced inflammatory response and cell apoptosis. miR-144-3p was upregulated while Caveolin-2 was downregulated in response to LPS treatment. Inflammation and cell apoptosis induced by LPS can be alleviated by miR-144-3p antagomir injection, but enhanced by miR-144-3p agomir or sh-Caveolin-2 treatment. miR-144-3p can negatively target Caveolin-2. miR-144-3p can activate the JAK/STAT signal pathway through Caveolin-2 in septic ALI mouse.
Conclusion:
miR-144-3 can promote LPS induced septic ALI through downregulating Caveolin-2 to activate the JAK/STAT signal pathway.
Insights
MicroRNA-144-3p promotes septic acute lung injury (ALI) by downregulating Caveolin-2 and activating the JAK/STAT pathway. This study elucidates a key mechanism in sepsis-induced lung damage.
Area of Science:
- Biomedical research
- Molecular biology
- Pathophysiology
Background:
- Sepsis-induced acute lung injury (ALI) is a critical condition with high mortality.
- The precise molecular mechanisms underlying septic ALI require further elucidation.
Purpose of the Study:
- To investigate the role and mechanism of microRNA-144-3p (miR-144-3p) in lipopolysaccharide (LPS)-induced septic ALI.
- To determine the relationship between miR-144-3p, Caveolin-2, and the JAK/STAT signaling pathway in septic ALI.
Main Methods:
- Establishment of a mouse model of septic ALI using LPS injection.
- Administration of miR-144-3p agomir, antagomir, or sh-Caveolin-2.
- Assessment of lung injury, inflammatory cytokine levels, and apoptosis.
- Analysis of miR-144-3p, Caveolin-2, and JAK/STAT pathway protein expression via qRT-PCR and Western blot.
- Dual luciferase reporter assay to confirm the interaction between miR-144-3p and Caveolin-2.
Main Results:
- LPS challenge led to increased lung W/W ratio, tissue damage, inflammation, and apoptosis.
- miR-144-3p expression was upregulated, while Caveolin-2 was downregulated following LPS treatment.
- miR-144-3p antagomir alleviated LPS-induced injury, whereas miR-144-3p agomir or sh-Caveolin-2 exacerbated it.
- miR-144-3p was found to directly target and downregulate Caveolin-2, subsequently activating the JAK/STAT pathway.
Conclusions:
- miR-144-3p plays a pro-inflammatory role in septic ALI.
- The mechanism involves the downregulation of Caveolin-2, leading to the activation of the JAK/STAT signaling pathway.
- Targeting miR-144-3p may represent a therapeutic strategy for managing septic ALI.
