Galectin-3-integrin α5β1 phase separation disrupted by advanced glycation end-products impairs diabetic wound healing in rodents.
Summary
Galectin-3 forms liquid–liquid phase-separated condensates with integrin α5β1 to activate FAK signaling and drive angiogenesis, a mechanism inhibited by advanced glycation end-products in diabetes. Topical recombinant galectin-3 delivered via hydrogel restored wound healing in rodent diabetes models without inducing systemic insulin resistance and synergized with insulin.
Key Findings
- Galectin-3 binds integrin α5β1 and forms liquid–liquid phase-separated condensates that enhance FAK phosphorylation and angiogenesis.
- Advanced glycation end-products bind galectin-3, blocking its interaction with integrin α5β1 and impairing angiogenesis in diabetic conditions.
- Topical recombinant galectin-3 in hydrogels accelerates wound healing in diabetic rodents without inducing systemic insulin resistance and synergizes with insulin.
Clinical Implications
Supports development of topical galectin-3 formulations to enhance angiogenesis and wound healing in diabetic foot ulcers, potentially combined with insulin, while minimizing systemic metabolic effects.
Why It Matters
Reveals a phase separation-based pro-angiogenic mechanism and provides a translational, local therapy concept for diabetic foot ulcers with in vivo efficacy.
Limitations
- Rodent models may not fully capture human diabetic wound complexity and comorbidities.
- Long-term safety, dosing, and manufacturing scalability of topical galectin-3 were not addressed.
Future Directions
Evaluate topical galectin-3 in large-animal and early-phase human trials, define optimal dosing and delivery matrices, and explore combination with standard wound care and glycemic control strategies.
Study Information
- Study Type
- Basic/Mechanistic Research
- Research Domain
- Pathophysiology/Treatment
- Evidence Level
- V - Preclinical mechanistic and in vivo rodent efficacy study
- Study Design
- OTHER