a Department of Biochemistry, Faculty of Medicine and Dentistry, 3-19 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada.
b Department of Biochemistry, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, 3-19 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Can J Physiol Pharmacol. 2019 Jun;97(6):486-492. doi: 10.1139/cjpp-2018-0525. Epub 2018 Nov 20.
A member of the matrix metalloproteinase family, matrix metalloproteinase-2 (MMP-2, gelatinase A), has been extensively studied for its role in both normal physiology and pathological processes. Whereas most research efforts in recent years have investigated the pathologies associated with MMP-2 overactivity, the pathological mechanisms elicited by MMP-2 underactivity are less well understood. Here, we distinguish between 2 states and describe their causes: () MMP-2 deficiency (complete loss of MMP-2 activity) and () MMP-2 insufficiency (defined as MMP-2 activity below baseline levels). Further, we review the biology of MMP-2, summarizing the current literature on MMP-2 underactivity in both mice and humans, and describe research being conducted by our lab towards improving our understanding of the pathological mechanisms elicited by MMP-2 deficiency/insufficiency. We think that this research could stimulate the discovery of new therapeutic approaches for managing pathologies associated with MMP-2 underactivity. Moreover, similar concepts could apply to other members of the matrix metalloproteinase family.
基质金属蛋白酶家族的一员，基质金属蛋白酶-2（MMP-2，明胶酶 A），因其在正常生理和病理过程中的作用而被广泛研究。尽管近年来大多数研究都集中在与 MMP-2 过度活跃相关的病理学上，但对 MMP-2 活性不足引起的病理机制了解较少。在这里，我们区分了两种状态并描述了它们的原因：（i）MMP-2 缺乏（完全丧失 MMP-2 活性）和（ii）MMP-2 不足（定义为 MMP-2 活性低于基线水平）。此外，我们回顾了 MMP-2 的生物学特性，总结了目前关于 MMP-2 在小鼠和人类中活性不足的文献，并描述了我们实验室正在进行的研究，以增进我们对 MMP-2 缺乏/不足引起的病理机制的理解。我们认为，这项研究可能会激发人们发现新的治疗方法来治疗与 MMP-2 活性不足相关的疾病。此外，类似的概念也可能适用于基质金属蛋白酶家族的其他成员。
