trans-4-(aminomethyl)cyclohexane carboxylic acid (T-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans
trans-4-(aminomethyl)cyclohexane carboxylic acid (T-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans
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DOI：
10.1111/1523-1747.ep12276640
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发表时间：
1997-07-01
影响因子：
6.5
通讯作者：
Feingold, KR
中科院分区：
文献类型：
--
作者：
Denda, M;Kitamura, K;Feingold, KR
由于创伤表皮增加蛋白水解活性，因为与屏障功能障碍相关的疾病具有升高的蛋白酶活性，我们研究了蛋白酶抑制剂对屏障恢复的时间过程和对由重复损伤诱导的表皮增生的发展的影响。在通过胶带剥离、丙酮处理或破坏屏障的洗涤剂（SDS）处理产生的表皮损伤后，单次应用5%氨甲环酸[4-（氨甲基）环己烷羧酸，t-AMCHA]（一种众所周知的抗纤溶酶试剂）加速无毛小鼠和人皮肤中的屏障恢复。相比之下，无论是氨基己酸，也不是氨基丁酸，非活性类似物的t-AMCHA，影响屏障恢复的时间过程。几种胰蛋白酶样丝氨酸蛋白酶抑制剂，例如，亮抑酶肽、TLCK和PMSF也加速屏障修复。相反，其他类型的蛋白酶抑制剂，例如，EDTA、胃酶抑制剂、N-乙基马来酰亚胺、凝乳酶抑制剂和TPCK没有加速屏障恢复。接下来，我们评估了每日局部施用t-AMCHA对表皮增生的影响，所述表皮增生由重复胶带剥离或丙酮处理诱导：持续7天。通过测量表皮厚度定量的增生程度在两种模型中通过重复应用t-AMCHA而降低。最后，在破坏屏障的表皮损伤后1-2小时，人和小鼠表皮中的蛋白水解活性增加。这些结果表明，纤溶酶，丝氨酸蛋白酶的抑制，加速屏障恢复和抑制由反复的屏障破坏诱导的表皮增生，可能通过降低伴随的表皮损伤的程度。
Because wounding the epidermis increases proteolytic activity and because disorders associated with barrier dysfunction have elevated protease activity, we studied the effect of protease inhibitors on the time course of barrier recovery and on the development of epidermal hyperplasia induced by repeated injury. After injuries to the epidermis produced by tape stripping, acetone treatment, or detergent (SDS) treatment that disrupt the barrier, a single application of 5% tranexamic acid [4-(aminomethyl)cyclohexane carboxylic acid, t-AMCHA], a well known anti-plasmin reagent, accelerated barrier recovery in both hairless mouse and human skin. In contrast, neither aminocaproic acid nor aminobutyric acid, inactive analogs of t-AMCHA, affected the time course of barrier recovery. Several trypsin-like serine protease inhibitors, e.g., leupeptin, TLCK, and PMSF, also accelerated barrier repair. In contrast other types of protease inhibitors, e.g., EDTA, pepstatin, N-ethylnaleimide, chymostatin, and TPCK, did not accelerate barrier recovery. We next evaluated the effects of daily topical application of t-AMCHA on epidermal hyperplasia, induced by repeated tape stripping or acetone treatment: for 7 d. The degree of hyperplasia, quantified by the measurement of epidermal thickness, was reduced in both models by repeated applications of t-AMCHA. Finally, proteolytic activity in both human and mouse epidermis increased 1-2 h after epidermal injuries that disrupt the barrier. These results demonstrate that the inhibition of plasmin, a serine protease, accelerates barrier recovery and inhibits the epidermal hyperplasia induced by repeated barrier disruption, perhaps by decreasing the extent of attendant epidermal injury.