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Updated: Jan 3, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Hydrogen treatment prevents lipopolysaccharide-induced pulmonary endothelial cell dysfunction through RhoA inhibition
Yuan Li1, Hongguang Chen2, Ruichen Shu1
1Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, PR China.
Background:
Pulmonary microvascular endothelial cells (PMVECs) are initial targets of sepsis-induced acute lung injury (ALI). During the apoptosis of PMVECs, tight junctions (TJ) and adherens junctions (AJ) are firstly damaged. Previous studies have suggested hydrogen treatment can protect lung microvasculature of mice from sepsis-induced endothelial dysfunction and maintain the coherence of pulmonary endothelium, but the underlying mechanism remains unclear.
Methods:
We investigated the role of hydrogen-rich medium on regulating intercellular junction proteins under lipopolysaccharide (LPS) treatment which mimicked sepsis in vitro. Changes of cytoskeleton regulatory protein ROCK and RhoA as well as PMVEC apoptotic rate were examined.
Results:
LPS treatment reduced the expression levels of occludin and VE-cadherin in PMVECs, while hydrogen-rich medium can recover these changes. Furthermore, H2 can significantly ameliorate the excessive expression of ROCK and RhoA under sepsis-mimicking condition. The application of RhoA activator U-46619 resulted in a more significant elevation in cell apoptotic rate as well as reduction in the expression of junctional proteins. Using H2 can almost completely inhibit the effects of RhoA activator.
Conclusions:
Our findings suggest that RhoA is a crucial protein in the signaling pathway of LPS-induced endothelial cell dysfunction. Hydrogen treatment can prevent LPS-induced junctional injury and cell death by inhibiting the activity of RhoA.
Insights
Hydrogen treatment protects against sepsis-induced lung injury by preserving endothelial cell junctions. It inhibits RhoA signaling, preventing cell death and maintaining vascular integrity.
Area of Science:
- Cell Biology
- Endothelial Cell Biology
- Sepsis Research
Background:
- Pulmonary microvascular endothelial cells (PMVECs) are primary targets in sepsis-induced acute lung injury (ALI).
- Sepsis disrupts tight junctions (TJ) and adherens junctions (AJ) in PMVECs.
- Hydrogen's protective effects on sepsis-induced lung injury are known, but mechanisms are unclear.
Purpose of the Study:
- To investigate hydrogen-rich medium's role in regulating intercellular junction proteins in PMVECs during sepsis.
- To examine the impact of hydrogen on cytoskeleton regulatory proteins ROCK and RhoA.
- To assess the effect of hydrogen on PMVEC apoptosis.
Main Methods:
- Lipopolysaccharide (LPS) treatment mimicked sepsis in vitro.
- Hydrogen-rich medium was used to treat PMVECs.
- Expression levels of occludin, VE-cadherin, ROCK, and RhoA were analyzed.
- PMVEC apoptotic rates were measured.
- RhoA activator (U-46619) was used to validate findings.
Main Results:
- LPS reduced occludin and VE-cadherin expression; hydrogen-rich medium restored these levels.
- Hydrogen ameliorated LPS-induced overexpression of ROCK and RhoA.
- RhoA activation exacerbated cell apoptosis and junctional protein loss.
- Hydrogen treatment inhibited the detrimental effects of RhoA activation.
Conclusions:
- RhoA is a key mediator in LPS-induced endothelial cell dysfunction.
- Hydrogen treatment prevents sepsis-induced endothelial junction injury and cell death.
- Inhibition of RhoA activity by hydrogen is a crucial protective mechanism.
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