Martins-Green Manuela, Petreaca Melissa, Wang Lei
Department of Cell Biology and Neuroscience, University of California , Riverside, California.
Adv Wound Care (New Rochelle). 2013 Sep;2(7):327-347. doi: 10.1089/wound.2012.0380.
Normal wound healing progresses through a series of overlapping phases, all of which are coordinated and regulated by a variety of molecules, including chemokines. Because these regulatory molecules play roles during the various stages of healing, alterations in their presence or function can lead to dysregulation of the wound-healing process, potentially leading to the development of chronic, nonhealing wounds.
A discovery that chemokines participate in a variety of disease conditions has propelled the study of these proteins to a level that potentially could lead to new avenues to treat disease. Their small size, exposed termini, and the fact that their only modifications are two disulfide bonds make them excellent targets for manipulation. In addition, because they bind to G-protein-coupled receptors (GPCRs), they are highly amenable to pharmacological modulation.
Chemokines are multifunctional, and in many situations, their functions are highly dependent on the microenvironment. Moreover, each specific chemokine can bind to several GPCRs to stimulate the function, and both can function as monomers, homodimers, heterodimers, and even oligomers. Activation of one receptor by any single chemokine can lead to desensitization of other chemokine receptors, or even other GPCRs in the same cell, with implications for how these proteins or their receptors could be used to manipulate function.
Investment in better understanding of the functions of chemokines and their receptors in a local context can reveal new ways for therapeutic intervention. Understanding how different chemokines can activate the same receptor and could identify new possibilities for drug development based on their heterotypic interactions.
正常伤口愈合通过一系列重叠阶段进行，所有这些阶段都由包括趋化因子在内的多种分子协调和调节。由于这些调节分子在愈合的各个阶段发挥作用，它们的存在或功能改变会导致伤口愈合过程失调，可能导致慢性不愈合伤口的形成。
趋化因子参与多种疾病状态的发现将这些蛋白质的研究推进到一个可能带来新治疗途径的水平。它们体积小、末端暴露，且唯一的修饰是两个二硫键，这使其成为理想的操作靶点。此外，由于它们与G蛋白偶联受体（GPCRs）结合，因此非常适合进行药理学调节。
趋化因子具有多种功能，在许多情况下，它们的功能高度依赖于微环境。此外，每种特定趋化因子可与多种GPCRs结合以刺激其功能，两者均可作为单体、同二聚体、异二聚体甚至寡聚体发挥作用。任何单一趋化因子激活一种受体可导致其他趋化因子受体甚至同一细胞中的其他GPCRs脱敏，这对如何利用这些蛋白质或其受体来操纵功能具有重要意义。
加大对趋化因子及其受体在局部环境中功能的了解力度，可能会揭示治疗干预的新方法。了解不同趋化因子如何激活同一受体，可能会基于它们的异型相互作用确定药物开发的新可能性。
