Powell Bethany S, Dhaher Yasin Y, Szleifer Igal G
Department of Biomedical Engineering, Northwestern University, Evanston, IL.
Department of Biomedical Engineering, Northwestern University, Physical Medicine and Rehabilitation Department, Evanston, IL, and Rehabilitation Institute of Chicago, Sensory Motor Performance Program, Chicago, IL.
Crit Rev Biomed Eng. 2015;43(5-6):401-28. doi: 10.1615/CritRevBiomedEng.2016016590.
Collagenases and gelatinases regulate many physiological processes and are involved in the pathogenesis and progression of various disease states, such as osteoarthritis, renal fibrosis, and atherosclerosis. These enzymes belong to the matrix metalloproteinase (MMP) family and are regulated by a number of factors, including sex hormones. Estrogen, relaxin, and progesterone can alter the balance between tissue degradation and repair by modulating MMPs, leading to gender disparities in many MMP-related disease states. In these diseases, MMPs initiate collagen degradation at the nanoscale when they cleave and denature collagen molecules. However, the net effect on tissue is generally observed at the macroscale. To understand how nanoscale events lead to macroscale changes, we must examine the intermediate scales. In this article, we review the literature that examines the effects of estrogen, relaxin, and progesterone on MMP production and activity, connecting the nanoscale, microscale, and macroscale details to relevant disease states.
胶原酶和明胶酶调节许多生理过程，并参与各种疾病状态的发病机制和进展，如骨关节炎、肾纤维化和动脉粥样硬化。这些酶属于基质金属蛋白酶（MMP）家族，并受多种因素调节，包括性激素。雌激素、松弛素和孕酮可通过调节MMP来改变组织降解与修复之间的平衡，从而导致许多与MMP相关的疾病状态出现性别差异。在这些疾病中，MMP在纳米尺度上切割并使胶原分子变性时启动胶原降解。然而，对组织的总体影响通常在宏观尺度上观察到。为了理解纳米尺度事件如何导致宏观尺度变化，我们必须研究中间尺度。在本文中，我们综述了研究雌激素、松弛素和孕酮对MMP产生和活性影响的文献，将纳米尺度、微观尺度和宏观尺度的细节与相关疾病状态联系起来。
