The role of the beta2-adrenoceptor in wound scarring

伤口愈合是一个复杂的过程，需要多个过程协同激活。进化引发了快速愈合成人伤口的反应，但并不完美，导致了疤痕的形成。伤口中高水平的促纤维化化学信号会促进过度的炎症和真皮成纤维细胞的活性，并导致伤口瘢痕形成。然而，在胚胎中，低水平的促纤维化化学信号和高水平的抗纤维化化学信号缓和了这些过程，并确保伤口完美再生。在发达国家，每年有1亿患者因择期手术、创伤和烧伤而愈合疤痕，导致严重的美容和功能问题，可能会使人在情感和身体上虚弱，并给医疗保健系统带来沉重的经济负担。目前还没有经过临床测试的药物可以防止伤口疤痕的发生。以前，我已经证明了皮肤中存在一个功能性的β2-肾上腺素能受体(B2AR)网络，但B2AR在伤口瘢痕形成中的作用尚不清楚。初步数据显示，B2ARs的激活改变了伤口中化学信号的平衡，达到了胚胎伤口中的水平，在胚胎伤口中，伤口愈合时没有疤痕。事实上，B2AR激动剂可以减少伤口炎症，降低伤口真皮成纤维细胞的活性。相反，B2AR拮抗剂将化学信号的平衡向相反的方向移动，并增强伤口中的成纤维细胞活性。B2AR激动剂能够改变伤口中化学鸡尾酒的组成，使其与胚胎中的成分相似，再加上它们减少炎症和成纤维细胞活性的能力，支持它们作为一种抗瘢痕治疗的研究。众所周知，B2AR激动剂是安全、耐受性良好的药物，长期用于治疗哮喘证明了这一点，并可能作为未来减少伤口疤痕的一种治疗方法具有重大潜力。在这里，我们描述了一项概念验证研究，以确定B2AR激动剂是否可以减少伤口疤痕。我们还使用适当的模型来研究这些生理过程，以探索集中研究的潜在机制。这一结果将有助于更好地了解伤口愈合和瘢痕形成的生理过程，并有望开发出一种预防患者伤口瘢痕形成的治疗方法。

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.