Soluble E-cadherin contributes to inflammation in acute lung injury via VEGF/VEGFR2 signaling.
Summary
sE-cadherin levels were elevated in ARDS patients and LPS-injured mice. Neutralizing sE-cadherin or inhibiting VEGF/VEGFR2 signaling attenuated lung inflammation, indicating that sE-cadherin drives ALI/ARDS inflammation via VEGF/VEGFR2 and may be a therapeutic target.
Key Findings
- sE-cadherin levels increased in ARDS patients and in LPS-exposed mice.
- Neutralizing sE-cadherin (DECMA-1) reduced LPS-induced lung inflammation in vivo.
- Exogenous sE-cadherin upregulated VEGF in human macrophages; intratracheal sE-cadherin increased neutrophil infiltration and IL-6/IL-1β, which were attenuated by VEGF/VEGFR2 inhibition.
Clinical Implications
sE-cadherin could serve as a biomarker and therapeutic target; strategies blocking sE-cadherin or VEGF/VEGFR2 warrant translational evaluation in ARDS.
Why It Matters
Reveals a targetable pathway (sE-cadherin→VEGF/VEGFR2) linking epithelial injury to inflammatory amplification in ALI/ARDS with convergent human and preclinical evidence.
Limitations
- Preclinical models (LPS) may not fully recapitulate human ARDS heterogeneity
- Patient sample size and clinical outcome correlations were not specified in the abstract
Future Directions
Validate sE-cadherin as a prognostic/theranostic biomarker in clinical ARDS cohorts and assess anti-sE-cadherin or VEGFR2 inhibitors in translational/early-phase trials.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- IV - Human case-control biomarker comparisons complemented by preclinical in vivo and in vitro experiments
- Study Design
- OTHER