The antimicrobial peptide LL-37 accelerated wound healing in diabetic mice by switching on TFEB-dependent autophagy, a cellular cleanup process that promotes skin cell migration.
TFEB-dependent autophagyLL-37's wound-healing mechanism works by activating this cellular cleanup pathway, with three key autophagy genes (ATG5, ATG7, BECN1) upregulated
What the researchers found
LL-37 accelerated diabetic wound healing by activating TFEB nuclear translocation, which upregulated autophagy markers ATG5, ATG7, and BECN1. Blocking autophagy or TFEB reversed LL-37's healing effects.
Why it matters
Diabetic wound healing is one of the most costly and common complications of diabetes, often leading to amputation. Understanding that LL-37 works through autophagy opens up new therapeutic approaches — either LL-37-based wound treatments or drugs that activate the same TFEB/autophagy pathway.
The numbers in context
LL-37 activated TFEB and downstream autophagy markers. Blocking autophagy reduced LL-37's healing benefits in diabetic wound models.
How the study worked
Full-thickness wound closure model in diabetic mice treated with LL-37 and/or autophagy inhibitor 3-MA. In vitro keratinocyte migration assays under high glucose conditions. TFEB activation measured by western blot and immunofluorescence; TFEB knockdown confirmed mechanism.
Who was studied
Diabetic mice with wound models
What this study cannot tell us
Mouse study — diabetic mouse wounds differ from human chronic diabetic ulcers, which involve more complex vascular and neuropathic factors. The relative contribution of autophagy versus LL-37's antimicrobial and anti-inflammatory activities wasn't fully quantified.
How to read the evidence
Preliminary evidence from animal and in vitro experiments. The mechanism is well-characterized but has not been validated in human clinical trials.
When this study was published
Published in 2024; represents current understanding of LL-37's wound-healing mechanisms.
The bigger picture
LL-37 is one of the most studied human antimicrobial peptides, with known antimicrobial, anti-inflammatory, and pro-healing properties. Pinpointing autophagy as a key mechanism adds scientific precision to therapeutic development. Since autophagy declines with age and in diabetes, treatments that restore it could address the root cause of impaired healing rather than just treating symptoms.
Questions still open
- Would topical LL-37 application be effective for human diabetic wound healing in clinical trials?
- Could other autophagy activators substitute for LL-37 in promoting diabetic wound healing?
- Does the TFEB-autophagy pathway also explain LL-37's healing effects in non-diabetic wounds?
Common questions
What is LL-37 and is it available as a treatment?
Why do diabetic wounds heal so poorly?
Read the original research
Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy.
Peptides, 175, 171183
Citation
Xi, Liuqing; Du, Juan; Xue, Wen; Shao, Kan; Jiang, Xiaohong; Peng, Wenfang; Li, Wenyi; Huang, Shan. (2024). Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy.. Peptides, 175, 171183. https://doi.org/10.1016/j.peptides.2024.171183