Inhibition of S100A12 Attenuates LPS-Induced Endothelial Barrier Dysfunction in HPMECs through the JAK2/STAT3 Signaling Pathway.
Total: 63.0Innovation: 7Impact: 6Rigor: 6Citation: 6
Summary
In LPS-injured HPMECs, S100A12 was upregulated and its inhibition reduced apoptosis, inflammation, and barrier disruption, restoring VE-cadherin/occludin and tube formation. Transcriptomics and Western blots implicated JAK2/STAT3 signaling as the key pathway mediating S100A12 effects.
Key Findings
- S100A12 expression significantly increased in LPS-stimulated HPMECs.
- S100A12 knockdown reduced apoptosis, inflammation, and endothelial barrier dysfunction, restoring VE-cadherin and occludin and tube formation.
- Transcriptomics and validation implicated JAK2/STAT3 signaling as the enriched pathway mediating S100A12 effects.
Clinical Implications
While preclinical, S100A12 and JAK2/STAT3 components may serve as biomarkers or therapeutic targets to preserve endothelial barrier function in ALI/ARDS.
Why It Matters
Identifies S100A12-JAK2/STAT3 signaling as a driver of endothelial barrier failure in ALI/ARDS models, suggesting a tractable target for vascular protection.
Limitations
- In vitro single-cell-type model; lacks in vivo validation
- LPS injury model may not capture full ARDS complexity
Future Directions
Validate S100A12 targeting in animal ALI/ARDS models; assess pharmacologic inhibitors and biomarker potential; test JAK2/STAT3 modulation in vivo.
Study Information
- Study Type
- Basic/mechanistic experiment (in vitro)
- Research Domain
- Pathophysiology
- Evidence Level
- V - In vitro mechanistic study without animal or human clinical outcomes
- Study Design
- OTHER