The role of the beta2-adrenoceptor in wound scarring
β2-肾上腺素受体在伤口疤痕中的作用
基本信息
- 批准号:G0901844/1
- 负责人:
- 金额:$ 38.85万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2010
- 资助国家:英国
- 起止时间:2010 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
伤口愈合是一个复杂的过程,需要许多过程的激活。进化已经引发了快速愈合成人伤口的反应,但不完美,导致疤痕形成。伤口中高水平的促纤维化化学信号促进过度炎症和真皮成纤维细胞活性,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调节这些过程,并确保伤口完美再生。在发达国家,每年有1亿名患者因择期手术、创伤和烧伤而愈合,造成严重的美容和功能问题,这些问题可能使人身心虚弱,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试验的药物可用于预防伤口瘢痕的发生。以前,我已经证明了一个功能性β 2-肾上腺素受体(B2 AR)网络存在于皮肤中,但B2 AR在伤口瘢痕形成中的作用是未知的。初步数据显示,B2 ARs激活改变了伤口中化学信号的平衡,使其达到胚胎伤口中的水平,其中伤口愈合而无疤痕。事实上,B2 AR激动剂减少伤口炎症并降低伤口中的真皮成纤维细胞活性。相反,B2 AR拮抗剂将化学信号的平衡向相反方向移动,并增强伤口中的成纤维细胞活性。B2 AR激动剂改变伤口中化学混合物的组成以类似于胚胎中发现的化学混合物的能力,以及它们减少炎症和成纤维细胞活性的能力,支持它们作为抗瘢痕形成治疗的研究。已知B2 AR激动剂是安全的、耐受性良好的药物,其长期用于治疗哮喘证明了这一点,并且可能具有作为减少伤口瘢痕形成的未来治疗的显著潜力。在这里,我们描述了一个概念验证研究,以确定是否B2 AR激动剂可以减少伤口疤痕。我们还探索了潜在的机制,在重点研究中使用适当的模型来研究这些生理过程。结果将导致更好地理解伤口愈合和瘢痕形成的生理过程,并有望导致治疗的发展,以防止患者的伤口瘢痕形成。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Christine Pullar其他文献
Christine Pullar的其他文献
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{{ truncateString('Christine Pullar', 18)}}的其他基金
The development of topical Salbutamol to prevent human skin scarring and hyperpigmentation
开发局部用沙丁胺醇预防人类皮肤疤痕和色素沉着过度
- 批准号:
MR/M024679/1 - 财政年份:2015
- 资助金额:
$ 38.85万 - 项目类别:
Research Grant
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