Modeling the effects of transforming growth factor-β on extracellular matrix alignment in dermal wound repair
Modeling the effects of transforming growth factor-β on extracellular matrix alignment in dermal wound repair
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DOI：
10.1046/j.1524-475x.2001.00278.x
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发表时间：
2001-07-01
影响因子：
2.9
通讯作者：
Maini, PK
中科院分区：
文献类型：
--
作者：
Dallon, JC;Sherratt, JA;Maini, PK
我们提出了一种新的皮肤创伤愈合过程中胶原沉积和排列的数学模型，着重于转化生长因子-β的调节作用。我们的工作扩展了以前开发的模型，该模型考虑了成纤维细胞和由胶原和纤维蛋白为基础的血液凝块组成的细胞外基质之间的相互作用，允许成纤维细胞定向胶原基质，产生和降解细胞外基质，而基质指导成纤维细胞并控制它们的速度。在这里，我们扩展了该模型，允许不同浓度的转化生长因子β改变成纤维细胞的性质。因此，我们能够模拟改变转化生长因子β曲线的实验。在这个模型框架内，我们发现大多数已知的转化生长因子β的作用，即细胞运动、细胞增殖和胶原产生的变化，对基质的排列并不重要，并且不能解释转化生长因子β的抗瘢痕特性。然而，我们发现，通过改变成纤维细胞的重定向率，与实验证据一致，再生组织的排列可以显著改变。这些数据为实验观察到的转化生长因子β对瘢痕形成的影响提供了解释。
We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGF beta) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracellular matrix composed of collagen and a fibrin based blood clot, by allowing fibroblasts to orient the collagen matrix, and produce and degrade the extracellular matrix, while the matrix directs the fibroblasts and control their speed, Here we extend the model by allowing a time varying concentration of TGF beta to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGF beta profile. Within this model framework we find that most of the known effects of TGF beta, i.e., changes in cell motility, cell proliferation and collagen production, are of minor Importance to matrix alignment and cannot explain the anti-scarring properties of TGF beta. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. These data provide an explanation for the experimentally observed influence of TGF beta on scarring.