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整合素与伤口愈合

Integrins in Wound Healing.

作者信息

Koivisto Leeni, Heino Jyrki, Häkkinen Lari, Larjava Hannu

机构信息

Laboratory of Periodontal Biology, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia , Vancouver, Canada .

Department of Biochemistry, University of Turku , Turku, Finland .

出版信息

Adv Wound Care (New Rochelle). 2014 Dec 1;3(12):762-783. doi: 10.1089/wound.2013.0436.

Abstract

Regulation of cell adhesions during tissue repair is fundamentally important for cell migration, proliferation, and protein production. All cells interact with extracellular matrix proteins with cell surface integrin receptors that convey signals from the environment into the nucleus, regulating gene expression and cell behavior. Integrins also interact with a variety of other proteins, such as growth factors, their receptors, and proteolytic enzymes. Re-epithelialization and granulation tissue formation are crucially dependent on the temporospatial function of multiple integrins. This review explains how integrins function in wound repair. Certain integrins can activate latent transforming growth factor beta-1 (TGF-β1) that modulates wound inflammation and granulation tissue formation. Dysregulation of TGF-β1 function is associated with scarring and fibrotic disorders. Therefore, these integrins represent targets for therapeutic intervention in fibrosis. Integrins have multifaceted functions and extensive crosstalk with other cell surface receptors and molecules. Moreover, in aberrant healing, integrins may assume different functions, further increasing the complexity of their functionality. Discovering and understanding the role that integrins play in wound healing provides an opportunity to identify the mechanisms for medical conditions, such as excessive scarring, chronic wounds, and even cancer. Integrin functions in acute and chronic wounds should be further addressed in models better mimicking human wounds Application of any products in acute or chronic wounds will potentially alter integrin functions that need to be carefully considered in the design.

摘要

组织修复过程中细胞黏附的调节对于细胞迁移、增殖和蛋白质产生至关重要。所有细胞通过细胞表面整合素受体与细胞外基质蛋白相互作用,这些受体将环境信号传递至细胞核,调节基因表达和细胞行为。整合素还与多种其他蛋白质相互作用,如生长因子、其受体和蛋白水解酶。再上皮化和肉芽组织形成关键依赖于多种整合素的时空功能。本综述解释了整合素在伤口修复中的作用。某些整合素可激活潜在的转化生长因子β1(TGF-β1),后者调节伤口炎症和肉芽组织形成。TGF-β1功能失调与瘢痕形成和纤维化疾病相关。因此,这些整合素是纤维化治疗干预的靶点。整合素具有多方面功能,并与其他细胞表面受体和分子存在广泛的相互作用。此外,在异常愈合过程中,整合素可能发挥不同功能,进一步增加了其功能的复杂性。发现并理解整合素在伤口愈合中的作用为确定诸如过度瘢痕形成、慢性伤口甚至癌症等医学状况的机制提供了契机。在更好模拟人类伤口的模型中应进一步研究整合素在急性和慢性伤口中的功能。在急性或慢性伤口中应用任何产品都可能改变整合素功能,这在设计时需要仔细考虑。

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