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分泌型热休克蛋白90(Hsp90)在伤口愈合中的作用——它如何塑造未来的治疗方法?

The role of secreted heat shock protein-90 (Hsp90) in wound healing - how could it shape future therapeutics?

作者信息

Guo Jiacong, Chang Cheng, Li Wei

机构信息

a Department of Dermatology and the Norris Comprehensive Cancer Centre , University of Southern California Keck Medical Centre , Los Angeles , CA , USA.

出版信息

Expert Rev Proteomics. 2017 Aug;14(8):665-675. doi: 10.1080/14789450.2017.1355244. Epub 2017 Jul 31.

Abstract

Defects in tissue repair or wound healing pose a clinical, economic and social problem worldwide. Despite decades of studies, there have been few effective therapeutic treatments. Areas covered: We discuss the possible reasons for why growth factor therapy did not succeed. We point out the lack of human disorder-relevant animal models as another blockade for therapeutic development. We summarize the recent discovery of secreted heat shock protein-90 (Hsp90) as a novel wound healing agent. Expert commentary: Wound healing is a highly complex and multistep process that requires participations of many cell types, extracellular matrices and soluble molecules to work together in a spatial and temporal fashion within the wound microenvironment. The time that wounds remain open directly correlates with the clinical mortality associated with wounds. This time urgency makes the healing process impossible to regenerate back to the unwounded stage, rather forces it to take many shortcuts in order to protect life. Therefore, for therapeutic purpose, it is crucial to identify so-called 'driver genes' for the life-saving phase of wound closure. Keratinocyte-secreted Hsp90α was discovered in 2007 and has shown the promise by overcoming several key hurdles that have blocked the effectiveness of growth factors during wound healing.

摘要

组织修复或伤口愈合缺陷在全球范围内构成了一个临床、经济和社会问题。尽管经过了数十年的研究,但有效的治疗方法仍然很少。涵盖领域:我们讨论了生长因子治疗未成功的可能原因。我们指出缺乏与人类疾病相关的动物模型是治疗发展的另一个障碍。我们总结了最近发现的分泌型热休克蛋白90(Hsp90)作为一种新型伤口愈合剂。专家评论:伤口愈合是一个高度复杂的多步骤过程,需要多种细胞类型、细胞外基质和可溶性分子在伤口微环境中以时空方式协同作用。伤口开放的时间与伤口相关的临床死亡率直接相关。这种时间紧迫性使得愈合过程无法恢复到未受伤阶段,而是迫使它采取许多捷径以保护生命。因此,出于治疗目的,识别伤口闭合的挽救生命阶段的所谓“驱动基因”至关重要。角质形成细胞分泌的Hsp90α于2007年被发现,并通过克服了几个阻碍伤口愈合过程中生长因子有效性的关键障碍而展现出前景。

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