Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes.
Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes.
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DOI：
10.1039/c8ib00048d
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发表时间：
2018-10-15
期刊：
影响因子：
--
通讯作者：
Long M
中科院分区：
文献类型：
--
作者：
Andasari V;Lü D;Swat M;Feng S;Spill F;Chen L;Luo X;Zaman M;Long M
角质形成细胞的迁移在创面再上皮化过程中起着至关重要的作用。该功能的缺陷会导致伤口复发，从而导致严重的临床问题。一些体外研究表明，表皮生长因子（EGF）可以调节角质形成细胞迁移的速度，从而影响角质形成细胞整合素的表达。由EGF刺激的整联蛋白表达（通过细胞-基质粘附）和角质形成细胞迁移速度之间的关系不是线性的，因为由于整联蛋白表达增加而增加的粘附已经在实验上显示由于细胞速度对粘附的双相依赖性而减缓细胞迁移。在我们以前的工作中，我们表明，角质形成细胞与EGF增强的成纤维细胞共培养形成不对称的迁移模式，其中，角质形成细胞向成纤维细胞迁移的累积距离小于从成纤维细胞迁移的距离。这种不对称模式被认为是由成纤维细胞分泌的高EGF浓度引起的。EGF通过旁分泌信号刺激角质形成细胞表面上的整合素受体的表达向成纤维细胞迁移。在本文中，我们提出了一个计算模型的角质形成细胞的迁移是由成纤维细胞分泌的EGF使用细胞波茨模型（CPM）。我们的计算模拟结果证实了实验中观察到的不对称模式。这些结果提供了一个更深入的了解我们的角质形成细胞迁移的复杂性在生长因子梯度的存在下，并可能解释受损的伤口愈合中的再上皮化失败。
It is widely agreed that keratinocyte migration plays a crucial role in wound re-epithelialization. Defects in this function contribute to wound reoccurrence causing significant clinical problems. Several in vitro studies have shown that the speed of migrating keratinocytes can be regulated by epidermal growth factor (EGF) which affects keratinocyte’s integrin expression. The relationship between integrin expression (through cell-matrix adhesion) stimulated by EGF and keratinocyte migration speed is not linear since increased adhesion, due to increased integrin expression, has been experimentally shown to slow down cell migration due to the biphasic dependence of cell speed on adhesion. In our previous work we showed that keratinocytes that were co-cultured with EGF-enhanced fibroblasts formed an asymmetric migration pattern, where, the cumulative distances of keratinocytes migrating toward fibroblasts were smaller than those migrating away from fibroblasts. This asymmetric pattern is thought to be provoked by high EGF concentration secreted by fibroblasts. The EGF stimulates the expression of integrin receptors on the surface of keratinocytes migrating toward fibroblasts via paracrine signaling. In this paper, we present a computational model of keratinocyte migration that is controlled by EGF secreted by fibroblasts using the Cellular Potts Model (CPM). Our computational simulation results confirm the asymmetric pattern observed in experiments. These results provide a deeper insight into our understanding of the complexity of keratinocyte migration in the presence of growth factor gradients and may explain re-epithelialization failure in impaired wound healing.
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DOI：
10.1083/jcb.201702025
发表时间：
2017-04-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dornier E;Norman JC
通讯作者：
Norman JC
影响因子：
6.5
作者：
ANDO, Y;JENSEN, PJ
通讯作者：
JENSEN, PJ
DOI：
10.1111/j.1524-4725.1992.tb03514.x
发表时间：
1992-07-01
期刊：
JOURNAL OF DERMATOLOGIC SURGERY AND ONCOLOGY
影响因子：
--
作者：
FALANGA, V;EAGLSTEIN, WH;CARSON, P
通讯作者：
CARSON, P
DOI：
10.1115/1.2796072
发表时间：
1997-05-01
影响因子：
1.7
作者：
Barocas, VH;Tranquillo, RT
通讯作者：
Tranquillo, RT
影响因子：
3.7
作者：
Caicedo-Carvajal CE;Shinbrot T;Foty RA
通讯作者：
Foty RA