The role of the beta2-adrenoceptor in wound scarring

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Wound healing is a complex process requiring the activation of numerous processes in concert. Evolution has primed responses to heal adult wounds quickly, but imperfectly, resulting in scar formation. High levels of pro-fibrotic chemical signals in the wound promote excessive inflammation and dermal fibroblast activity and result in wound scarring. However, in the embryo, low levels of pro-fibrotic chemical signals and high levels of anti-fibrotic chemical signals temper these processes and ensure that the wound regenerates perfectly. 100 million patients in the developed world heal with a scar every year as a result of elective procedures, trauma and burn injuries, causing serious cosmetic and functional problems that can be emotionally and physically debilitating and place a heavy financial burden on Health Care Systems. There are currently no clinically tested pharmaceuticals available to prevent the occurrence of wound scarring. Previously, I have demonstrated that a functional beta2-adrenoceptor (B2AR) network exists in the skin, but the role of the B2AR in wound scarring is unknown. Preliminary data shows that B2ARs activation alters the balance of chemical signals in the wound towards levels seen in embryonic wounds, where wounds heal without scars. Indeed, B2AR agonists reduce wound inflammation and reduce dermal fibroblast activity in wounds. In contrast, B2AR antagonists shift the balance of chemical signals in the opposite direction and enhance fibroblast activity in wounds. The ability of B2AR agonists to alter the composition of the chemical cocktail in the wound to resemble that found in the embryo, together with their ability to reduce inflammation and fibroblast activity, support their investigation as an anti-scarring treatment. B2AR agonists are known to be safe, well-tolerated pharmaceuticals evidenced by their long-standing use for the treatment of asthma and could have significant potential as a future treatment to reduce wound scarring. Here we describe a proof of concept study to determine if B2AR agonists can reduce wound scarring. We also explore the underlying mechanisms in focused studies using appropriate models to investigate these physiological processes. The results will lead to a better understanding of the physiological processes of wound healing and scarring and hopefully lead to the development of a treatment to prevent wound scarring in patients.