Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
Matrix Biol. 2015 May-Jul;44-46:138-46. doi: 10.1016/j.matbio.2015.01.018. Epub 2015 Jan 31.
Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction.
基质金属蛋白酶（MMPs）参与与感染、肿瘤、自身免疫性疾病和神经功能障碍相关的病理学。随着 MMPs 的上游调节剂——细胞外基质金属蛋白酶诱导因子（EMMPRIN，CD147）的鉴定，探讨 EMMPRIN 是否在中枢神经系统（CNS）疾病的病理学中发挥作用变得尤为重要。这将为更上游和更有效的治疗靶点提供可能性。事实上，包括神经胶质瘤、阿尔茨海默病（AD）、多发性硬化症（MS）在内的多种疾病，以及缺氧/缺血等其他损伤，均显示出 EMMPRIN 水平升高，与 MMP 产生相关。相比之下，鉴于 EMMPRIN 在 CNS 稳态中调节单羧酸转运蛋白（MCT）和与整合素等粘附分子相互作用的作用，我们需要考虑到 EMMPRIN 也可能发挥重要的调节或保护功能。这篇综述总结了目前对 EMMPRIN 参与 CNS 稳态的认识，包括其在加重或减轻神经损伤方面的可能作用，以及包括 MMP 诱导在内的 EMMPRIN 机制。
