A Critical Role for MALAT1 in Gram-negative Bacteria-induced Coagulation via Regulation of Caspase-11 signaling.
Summary
Plasma IFNβ at admission predicted 48-hour onset of septic DIC, and mechanistically IFNβ induces macrophage MALAT1, which suppresses GPX4, enhances caspase-11 activation, and promotes coagulation. Targeting the IFNβ–MALAT1–caspase-11 axis could enable early DIC risk stratification and novel interventions.
Key Findings
- Admission plasma IFNβ, but not HMGB1, correlates with 48-hour onset of septic DIC.
- IFNβ induces macrophage MALAT1, which lowers GPX4 activity via YY1/Hba-a1, facilitating LPS internalization and caspase-11 activation.
- Macrophage-specific Malat1 deletion protects against caspase-11/GSDMD–dependent phosphatidylserine exposure and bacteria-induced coagulation.
Clinical Implications
IFNβ could serve as an early biomarker for DIC risk, and MALAT1/caspase-11 signaling represents a therapeutic target to prevent sepsis-associated coagulopathy.
Why It Matters
Bridges human predictive biomarker data with mechanistic validation in gene-edited mice, uncovering a novel immunocoagulation pathway in bacterial sepsis.
Limitations
- Clinical cohort details (size, external validation) are limited in the abstract.
- Translational steps for targeting MALAT1/GPX4/caspase-11 in humans remain to be defined.
Future Directions
Prospective validation of IFNβ for DIC prediction, development of MALAT1/GPX4 modulators, and early-phase trials to prevent sepsis-associated coagulopathy.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- III - Observational case-control biomarker analysis with mechanistic support from animal models.
- Study Design
- OTHER