Connexin43 carboxyl-terminal peptides reduce scar progenitor and promote regenerative healing following skin wounding

Regen Med, 2009 · DOI: 10.2217/17460751.4.2.205 · Published: March 1, 2009

Regenerative Medicine Genetics Dermatology

Simple Explanation

This study investigates how a specific part of a protein called connexin43 (Cx43), when turned into a cell-penetrating peptide (ACT1), affects skin wound healing. The researchers looked at wound closure, inflammation, and tissue regeneration in mouse and pig skin after applying the ACT1 peptide. The main finding is that ACT1 promotes better healing with less scarring, potentially by reducing inflammation and altering the structure of Cx43 in skin cells.

Study Duration

30-90 days

Participants

Mice and pigs

Evidence Level

Not specified

Key Findings

1
Cx43 CT-peptide prompted decreases in area of scar progenitor tissue and promoted restoration of dermal histoarchitecture and mechanical strength following wounding of skin.
2
These changes in healing were preceded by peptide-induced reduction in inflammatory neutrophil infiltration and alterations in the organization of epidermal Cx43, including increased connexon aggregation.
3
ACT1 treatment prompted a partial re-establishment of vascularization in the superficial dermis following wounding.

Research Summary

The study demonstrates that a Cx43 carboxyl-terminal peptide (ACT1) can accelerate wound closure and improve the quality of skin healing in both mouse and pig models. ACT1 treatment leads to reduced inflammation, decreased scar tissue formation, and enhanced regeneration of skin structures such as rete pegs and blood vessels. The peptide appears to work by altering the organization of Cx43 within skin cells and reducing the infiltration of inflammatory cells into the wound area.

Practical Implications

Therapeutic Potential

Cx43 CT peptide promotes regenerative healing of cutaneous wounds and may have applications in tissues other than skin, including heart, cornea and spinal cord.

Implant Biocompatibility

Testing whether Cx43 CT peptides have therapeutic applications in implant biocompatibility.

Surgical Healing

The increases in rete pegs and improved mechanical characteristics of ACT1-treated wounds may thus have implications for healing of surgical lesions closed by primary intention.

Study Limitations

1
It remains to be determined whether this is the primary explanatory factor of mechanism.
2
The specifics of this novel mechanism remain to be elucidated.
3
Whether or how an increase in the relative amounts of Cx43 sequestrated in GJ aggregates leads to accelerated wound healing remains to be understood.

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