MFGE8 regulates the EndoMT of HLMECs through the BMP signaling pathway and fibrosis in acute lung injury.
Summary
Serum MFGE8 is reduced in ARDS and higher levels associate with better survival. MFGE8 restrains LPS-induced EndoMT in HLMECs via BMP/Smad signaling and reduces pulmonary fibrosis and EndoMT in a mouse ALI model, nominating MFGE8 as a biomarker and therapeutic target.
Key Findings
- Serum MFGE8 levels were significantly decreased in ARDS patients; higher levels correlated with better survival.
- rhMFGE8 attenuated LPS-induced EndoMT in HLMECs (↑CD31, ↓α-SMA), reducing invasion and migration.
- MFGE8 knockdown activated BMP/Smad1/5-Smad4 signaling and Snail, while rhMFGE8 inhibited these pathways.
- In vivo, rhMFGE8 ameliorated pulmonary fibrosis and EndoMT in a mouse acute lung injury model.
Clinical Implications
MFGE8 could aid risk stratification in ARDS and represents a candidate for anti-fibrotic therapy to limit EndoMT-driven remodeling after acute lung injury.
Why It Matters
This study links a measurable human biomarker to mechanistic control of EndoMT and fibrosis with in vivo efficacy, bridging pathophysiology and therapeutic potential in ARDS.
Limitations
- Clinical cohort size and adjustment for confounders were not detailed.
- Functional outcomes were limited to surrogate markers; long-term pulmonary function was not assessed.
Future Directions
Validate MFGE8 as a prognostic biomarker in large, multicenter ARDS cohorts; optimize dosing and timing of rhMFGE8; and test efficacy in sepsis-induced ARDS models.
Study Information
- Study Type
- Experimental study
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical and translational study with limited human observational data
- Study Design
- OTHER