Badola Sunita, Spurling Heidi, Robison Keith, Fedyk Eric R, Silverman Gary A, Strayle Jochen, Kapeller Rosana, Tsu Christopher A
Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139, USA.
Genomics. 2006 Aug;88(2):173-84. doi: 10.1016/j.ygeno.2006.03.017. Epub 2006 May 18.
Imbalanced protease activity has long been recognized in the progression of disease states such as cancer and inflammation. Serpins, the largest family of endogenous protease inhibitors, target a wide variety of serine and cysteine proteases and play a role in a number of physiological and pathological states. The expression profiles of 20 serpins and 105 serine and cysteine proteases were determined across a panel of normal and diseased human tissues. In general, expression of serpins was highly restricted in both normal and diseased tissues, suggesting defined physiological roles for these protease inhibitors. A high correlation in expression for a particular serpin-protease pair in healthy tissues was often predictive of a biological interaction. The most striking finding was the dramatic change observed in the regulation of expression between proteases and their cognate inhibitors in diseased tissues. The loss of regulated serpin-protease matched expression may underlie the imbalanced protease activity observed in pathological states.
蛋白酶活性失衡在癌症和炎症等疾病状态的发展过程中早已为人所知。丝氨酸蛋白酶抑制剂（Serpins）是内源性蛋白酶抑制剂中最大的家族，作用于多种丝氨酸和半胱氨酸蛋白酶，并在许多生理和病理状态中发挥作用。在一组正常和患病的人体组织中测定了20种丝氨酸蛋白酶抑制剂以及105种丝氨酸和半胱氨酸蛋白酶的表达谱。总体而言，丝氨酸蛋白酶抑制剂在正常组织和患病组织中的表达都受到高度限制，这表明这些蛋白酶抑制剂具有特定的生理作用。健康组织中特定丝氨酸蛋白酶抑制剂-蛋白酶对的表达高度相关，这通常预示着存在生物学相互作用。最显著的发现是在患病组织中观察到蛋白酶及其同源抑制剂之间表达调控的巨大变化。丝氨酸蛋白酶抑制剂-蛋白酶匹配表达调控的丧失可能是病理状态下观察到的蛋白酶活性失衡的基础。
