" By inhibiting the activation of Engrailed-1 (En1) in fibroblasts , the skin wounds of mice no longer form scars, but heal through regeneration, so that the skin restores normal hair follicles and glands, extracellular matrix and mechanical strength."
"Skin wounds are usually healed by scars. After the wound appears, fibroblasts expressing Engrailed-1 (En1) protein quickly move to the wound site, deposit and block the extracellular matrix, and form scars while healing the wound."
1. Scar skin lacks hair follicles, sebaceous glands and other skin accessories;
2. Scar skin contains dense, parallel extracellular matrix fibers;
3. Due to this matrix structure change, scar skin lacks the flexibility and strength of normal skin.
Only by solving the above three differences, restoring hair follicles, sebaceous glands and other skin attachments, rebuilding normal extracellular matrix structure, and restoring normal skin flexibility and strength, can this be considered a successful scar repair therapy.
Previous studies have known, scarring from wounds healing expression Engrailed-. 1 (En1) protein in fibroblasts , the scar is from the uninjured site to amplify En1 positive fibroblasts, or may be from the wound to the environment En1 Activation of negative fibroblasts.
The research team used fibroblast cell transplantation and transgenic mouse models to track En1 expression. The response of fibroblasts to mechanical forces in vitro and in vivo was also studied to establish a mechanical transduction mechanism that links skin tension with En1 expression.
Finally, verteporfin was used to inhibit the YAP gene, or knock down the YAP gene to regulate the expression of En1 during wound healing, and through RNA sequencing, quantitative histopathological comparison and mechanical strength testing, the experimental wound, uninjured skin and scar skin Make a comparison.
Fibroblast transplantation and lineage tracking studies have shown that En1 negative fibroblasts (ENF) in the deep dermal tissue activate En1 expression in the wound environment, producing about 40% to 50% scar fibroblasts. By inhibiting the YAP gene or knocking down the YAP gene by chemical inhibitors, En1 negative fibroblasts (ENF) will not activate En1.
In the wound process, the use of verteporfin to inhibit the YAP gene will block the activation of En1 and promote ENF-mediated repair, restore skin function within 30 days, and restore functional hair follicles and sebaceous glands.
The quantitative comparison of scars and regenerated skin shows that inhibition of YAP can induce normal skin ultrastructure recovery, thereby restoring normal skin mechanical strength.
The study also found that the use of diphtheria toxin to eliminate En1 positive fibroblasts, similar to knocking down the YAP gene of fibroblasts, promotes the restoration of normal skin structure. This indicates that the activation of En1 can be regulated directly or indirectly. Promote wound regeneration and inhibit the appearance of scars.
Another thing to add; Patents on Verteporfin have all expired so anyone can manufacture it. There are manufacturers selling >99% purity Verteporfin at better prices for research purposes, but they don't sell to patients.