McCall-Culbreath K D, Zutter M M
Department of Microbiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Curr Drug Targets. 2008 Feb;9(2):139-49. doi: 10.2174/138945008783502494.
Integrins are alphabeta heterodimeric receptors that connect the extracellular environment with intracellular signaling events. Integrins are important for normal development and function, but are also involved in the pathogenesis of diseases including cancer, autoimmunity and heart disease. We will review the present data on a family of integrins, the collagen receptors that include the alpha1beta1, alpha2beta1, alpha1beta1 and alpha1beta1 integrins. We will describe the knowledge gained from genetic deletion of each integrin in animal models. Mice lacking any single collagen receptor display no overt defect. However, studies using the alpha1beta1 and alpha2beta1 integrin-deficient mice indicate that these receptors play an important role in innate immunity, inflammation and autoimmunity. Finally, we will elucidate the interesting and sometimes overlapping roles for alpha1beta1 and alpha2beta1 integrins in disease and will propose potential stategies to therapeutically target these receptors to alleviate or treat disease.
整合素是αβ异二聚体受体,可将细胞外环境与细胞内信号转导事件联系起来。整合素对正常发育和功能很重要,但也参与包括癌症、自身免疫和心脏病在内的疾病发病机制。我们将综述关于整合素家族——包括α1β1、α2β1、α1β1和α1β1整合素的胶原蛋白受体的现有数据。我们将描述在动物模型中通过基因敲除每种整合素所获得的知识。缺乏任何一种胶原蛋白受体的小鼠均未表现出明显缺陷。然而,使用α1β1和α2β1整合素缺陷小鼠的研究表明,这些受体在固有免疫、炎症和自身免疫中起重要作用。最后,我们将阐明α1β1和α2β1整合素在疾病中有趣且有时重叠的作用,并提出针对这些受体进行治疗的潜在策略,以减轻或治疗疾病。