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Updated: Feb 8, 2026
Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
Published on: October 4, 2019
Connexin 43-Based Therapeutics for Dermal Wound Healing
Jade Montgomery1,2, Gautam S Ghatnekar3, Christina L Grek4
1Virginia Tech Carilion Research Institute, Roanoke, VA 24016, USA. jmont@vt.edu.
Abstract:
The most ubiquitous gap junction protein within the body, connexin 43 (Cx43), is a target of interest for modulating the dermal wound healing response. Observational studies found associations between Cx43 at the wound edge and poor healing response, and subsequent studies utilizing local knockdown of Cx43 found improvements in wound closure rate and final scar appearance. Further preclinical work conducted using Cx43-based peptide therapeutics, including alpha connexin carboxyl terminus 1 (αCT1), a peptide mimetic of the Cx43 carboxyl terminus, reported similar improvements in wound healing and scar formation. Clinical trials and further study into the mode of action have since been conducted on αCT1, and Phase III testing for treatment of diabetic foot ulcers is currently underway. Therapeutics targeting connexin activity show promise in beneficially modulating the human body’s natural healing response for improved patient outcomes across a variety of injuries.
Insights
Targeting connexin 43 (Cx43) shows promise for improving wound healing. Therapies like the alpha connexin carboxyl terminus 1 (αCT1) peptide enhance healing and scar appearance, with ongoing trials for diabetic foot ulcers.
Area of Science:
- Biochemistry
- Dermatology
- Regenerative Medicine
Background:
- Connexin 43 (Cx43) is a key gap junction protein involved in cellular communication.
- Cx43 expression at wound sites is linked to impaired dermal healing.
- Modulating Cx43 activity presents a therapeutic avenue for wound repair.
Purpose of the Study:
- To investigate the role of connexin 43 (Cx43) in dermal wound healing.
- To evaluate the efficacy of Cx43-targeting therapeutics in preclinical and clinical settings.
- To assess the potential of alpha connexin carboxyl terminus 1 (αCT1) for improving wound closure and scar quality.
Main Methods:
- Observational studies correlating Cx43 levels with healing outcomes.
- Preclinical studies involving local knockdown of Cx43.
- Preclinical and clinical evaluation of Cx43-based peptide therapeutics, specifically αCT1.
- Ongoing Phase III clinical trials for diabetic foot ulcers.
Main Results:
- Reduced Cx43 levels correlate with improved wound closure rates.
- Cx43-based peptide therapeutics, including αCT1, demonstrated enhanced wound healing and scar appearance in preclinical models.
- Clinical trials support the therapeutic potential of αCT1.
Conclusions:
- Connexin 43 (Cx43) is a viable therapeutic target for modulating dermal wound healing.
- Alpha connexin carboxyl terminus 1 (αCT1) peptide therapy shows significant promise for improving healing outcomes.
- Targeting connexin activity offers a novel strategy for enhancing patient recovery from various injuries, including diabetic foot ulcers.
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