Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA
Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA
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晚期糖基化终产物修饰的 BSA 对人角质形成细胞活动性和增殖的损害
DOI：
10.1007/s00403-010-1102-z
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发表时间：
2011-07
影响因子：
3
通讯作者：
严励
中科院分区：
文献类型：
--
作者：
严励
角质形成细胞的迁移和增殖对伤口再上皮化至关重要，并且该功能的缺陷与慢性不愈合伤口的临床现象相关。晚期糖基化终产物（AGEs）是糖尿病患者体内长寿命蛋白质发生非酶糖基化的产物，在糖尿病并发症中起重要作用。然而，AGEs在角质形成细胞迁移和增殖中的具体作用及其潜在的分子机制尚未完全确定。本研究的目的是阐明AGE修饰的牛血清白蛋白（AGE-BSA）与角质形成细胞之间的相互作用。结果，我们发现AGE-BSA与50 μg/ml的AGE-BSA孵育长达48小时对角质形成细胞的活力没有影响。AGE-BSA（但非糖化BSA）在一定浓度范围内对角质形成细胞迁移产生浓度依赖性抑制。AGE-BSA诱导角质形成细胞基质金属蛋白酶-9（MMP-9）表达上调，而基质金属蛋白酶组织抑制因子-1（TIMP-1）表达下调。AGE-BSA还显著抑制角质形成细胞中磷酸化粘着斑激酶Tyr 397（p-FAK）和α2β1整合素的表达，而总FAK表达水平保持不变。AGE-BSA孵育72 h后，角质形成细胞增殖能力减弱。综上所述，这些发现表明，在AGE-BSA的存在下，角质形成细胞失去其迁移和增殖能力。提示在糖尿病慢性高血糖背景下，AGE-BSA可能通过MMP-9/TIMP-1、p-FAK和α2β1整合素介导对角质形成细胞迁移的影响。
The migration and proliferation of keratinocytes is critical to wound re-epithelialization and defects in this function are associated with the clinical phenomenon of chronic non-healing wounds. Advanced glycation end products (AGEs) occur through non-enzymatic glycation of long-lived proteins in diabetes and play important roles in diabetic complications. However, specific roles for AGEs in keratinocyte migration and proliferation, and the underlying molecular mechanisms, have not been fully established. The aim of the current study was to elucidate the interaction between AGE-modified bovine serum albumin (AGE-BSA) and keratinocytes. As a result, we found that AGE-BSA had no effect on the viability of keratinocytes for up to 48 h of incubation with 50 μg/ml of AGE-BSA. AGE-BSA (but not non-glycated BSA) exerted a concentration-dependent suppression of keratinocyte migration at a range of concentrations. The expression of matrix metalloproteinase-9 (MMP-9) was significantly up-regulated in keratinocytes incubated with increasing AGE-BSA, but tissue inhibitor of metalloproteinases-1 (TIMP-1) expression was down-regulated. AGE-BSA also profoundly depressed phospho-focal adhesion kinase-Tyr397 (p-FAK) and α2β1 integrin expression, while total-FAK expression levels remained constant, in keratinocytes. The proliferative capacity of keratinocytes was diminished after 72 h AGE-BSA incubation. Taken together, these findings suggested that in the presence of AGE-BSA, keratinocytes lose their migratory and proliferation abilities. These data also indicated that, in the context of the chronic hyperglycemia in diabetes, the effects of AGE-BSA on keratinocyte migration might be mediated through MMP-9/TIMP-1, p-FAK and α2β1 integrin.
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影响因子：
4.4
作者：
Tokumaru, S;Sayama, K;Hashimoto, K
通讯作者：
Hashimoto, K
影响因子：
3.5
作者：
Nah, Seong-Su;Choi, In-Young;Lee, Chang-Keun
通讯作者：
Lee, Chang-Keun
影响因子：
5.1
作者：
A. S. Teixeira;M. Caliari;O. A. Rocha;R. D. Machado;S. P. Andrade
通讯作者：
A. S. Teixeira;M. Caliari;O. A. Rocha;R. D. Machado;S. P. Andrade
影响因子：
158.5
作者：
Yang, Wenying;Lu, Juming;He, Jiang
通讯作者：
He, Jiang
影响因子：
8
作者：
Scott, KA;Arnott, CH;Balkwill, FR
通讯作者：
Balkwill, FR