Thymosin β4 promotes matrix metalloproteinase expression during wound repair
Thymosin β4 promotes matrix metalloproteinase expression during wound repair
复制标题
DOI：
10.1002/jcp.20650
复制
发表时间：
2006-07-01
影响因子：
5.6
通讯作者：
Kleinman, Hynda K.
中科院分区：
文献类型：
--
作者：
Philp, Deborah;Scheremeta, Brooke;Kleinman, Hynda K.
行动不便的患者、糖尿病患者和老年人的伤口愈合受损。43个氨基酸的血管生成肽胸腺素β（4）（T β（4））先前已被发现加速大鼠、老年小鼠和db/db糖尿病小鼠的皮肤伤口修复。它还促进正常大鼠和小鼠的角膜修复。由于蛋白酶在伤口修复中很重要，我们假设T β 4可能调节参与伤口修复的细胞中基质金属蛋白酶（MMP）的表达。通过RT-PCR对受伤后第1、2和3天切除的小鼠整个真皮伤口进行分析表明，T β（4）在受伤后第2天增加了几种金属蛋白酶的表达，包括MMP-2和-9的表达，是对照组的几倍。我们进一步分析了伤口中正常存在的细胞对外源性T β 4的反应所分泌的金属蛋白酶。对培养的角质形成细胞、内皮细胞和成纤维细胞进行蛋白质印迹分析，结果显示，用浓度增加的T β（4）处理后，MMP-1、MMP-2和MMP-9的水平以细胞特异性方式增加。T β（4）还可促进活化单核细胞分泌MMP-1和MMP-9。中心肌动蛋白结合结构域，氨基酸17-23，具有金属蛋白酶诱导的所有活性。我们的结论是，T β（4）的伤口愈合活性部分在于其通过其中心肌动蛋白结合域增加蛋白酶活性的能力。因此，T β（4）可能在伤口修复期间细胞外基质重塑中发挥关键作用。
Immobilized patients, diabetics, and the elderly suffer from impaired wound healing. The 43-amino acid angiogenic peptide thymosin beta(4) (T beta(4)) has previously been found to accelerate dermal wound repair in rats, aged mice, and db/db diabetic mice. It also promotes corneal repair in both normal rats and mice. Because proteinases are important in wound repair, we hypothesized that T beta(4) may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Analysis by RT-PCR of whole excised mouse dermal wounds on days 1, 2, and 3 after wounding showed that T beta(4) increased several metalloproteinases, including MMP-2 and -9 expression by several-fold over control on day 2 after wounding. We further analyzed the metalloproteinases secreted in response to exogenous T beta(4) by cells normally present in the wound. Western blot analysis of cultured keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of T beta(4) showed increases in the levels of MMP-1, -2, and -9 in a cell-specific manner. T beta(4) also enhanced the secretion of MMP-1 and MMP-9 by activated monocytes. The central actin-binding domain, amino acids 17-23, had all of the activity for metalloproteinase induction. We conclude that part of the wound healing activity of T beta(4) resides in its abilityto increase proteinase activity via its central actin-binding domain. Thus, T beta(4) may play a pivotal role in extracellular matrix remodeling during wound repair.