Mechanical Stretch-Induced Interlayer Coordination between MMP2 and COL17A1 Exacerbates Regenerative Exhaustion in Skin
Sun Y., Qian Q., Xu L., Gao B., Li T., Li Y.
Animal Study, published in Adv Sci (Weinh) (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Adv Sci (Weinh) (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40960906
- PMCID
- PMC12591213
- DOI
- 10.1002/advs.202511474
- Citations
- 4
Abstract (original English)
The layered structure of skin necessitates highly sophisticated tissue coordination during regeneration. The unmet clinical need of long-term skin expansion therapy stems from limited regenerative capacity, yet the underlying mechanism remains enigmatic due to the lack of appropriate animal model. A mouse scalp-based mechanical stretch model is established that mimics clinical long-term skin expansion. Prolonged skin expansion progressively drives interfollicular epidermal stem cells towards a state of irreversible regenerative exhaustion, marked by impaired proliferation, differentiation, adhesion, and activity. Mechanistically, mechano-stress-induced accumulation of MMP2 in the dermis mediates a shift in extracellular matrix turnover from deposition to degradation, impairing stem cell activity, disrupting niche integrity, and simultaneously triggering proteolysis of COL17A1 at the interlayer. Restoring COL17A1, either through genetic overexpression or administration of Marimastat, a protease inhibitor, is sufficient to mitigate regenerative exhaustion. Consistently, in patient-derived skin samples, COL17A1 levels correlate with ECM integrity and regenerative potential. Combined, a new stretch-induced skin expansion model is established, revealing hidden components underlying regenerative exhaustion, and proposing Marimastat for drug repurposing. Restoration of COL17A1 is prop
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
How we grade evidenceBrowse all related research
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