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Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes
Andasari V1; Lv DY(吕东媛)2,3; Swat M4; Feng SL(冯世亮)2,3; Spill F1; Chen L5; Luo XD5; Zaman M1; Long M(龙勉)2,3,6
通讯作者Andasari, Vivi(andasari@bu.edu)
发表期刊INTEGRATIVE BIOLOGY
2018-10-01
卷号10期号:10页码:605-634
ISSN1757-9694
摘要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.
DOI10.1039/c8ib00048d
收录类别SCI
语种英语
WOS记录号WOS:000447503900004
关键词[WOS]EPIDERMAL-GROWTH-FACTOR ; LIGAND-BINDING AFFINITY ; COLON-CARCINOMA CELLS ; MIGRATION SPEED ; ADENOCARCINOMA CELLS ; MATHEMATICAL-MODEL ; INTEGRIN SUBUNIT ; BIOLOGICAL CELLS ; TISSUE COHESION ; POTTS-MODEL
WOS研究方向Cell Biology
WOS类目Cell Biology
资助项目Natural Science Foundation of China[31110103918] ; Natural Science Foundation of China[31470907] ; Natural Science Foundation of China[11502272] ; Chinese Academy of Sciences[XDA01030604] ; Chinese Academy of Sciences[XDA04020219] ; NIH[5U01CA177799] ; NIH[1U01 CA202123] ; NIH[P01HL 120839]
项目资助者Natural Science Foundation of China ; Chinese Academy of Sciences ; NIH
论文分区Q3
力学所作者排名2
RpAuthorAndasari, Vivi
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://dspace.imech.ac.cn/handle/311007/79068
专题微重力重点实验室
作者单位1.Boston Univ, Dept Biomed Engn, 44 Cummington Mall, Boston, MA 02215 USA;
2.Chinese Acad Sci, Ctr Biomech & Bioengn, Natl Micrograv Lab, Key Lab Micrograv, Beijing 100190, Peoples R China;
3.Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing 100190, Peoples R China;
4.Univ Penn, Computat Memory Lab, Philadelphia, PA 19104 USA;
5.Third Mil Med Univ, Southwest Hosp, Burn Res Inst, Chongqing 400038, Peoples R China;
6.Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714
Andasari V,Lv DY,Swat M,et al. Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes[J]. INTEGRATIVE BIOLOGY,2018,10,10,:605-634.
APA Andasari V.,吕东媛.,Swat M.,冯世亮.,Spill F.,...&龙勉.(2018).Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes.INTEGRATIVE BIOLOGY,10(10),605-634.
MLA Andasari V,et al."Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes".INTEGRATIVE BIOLOGY 10.10(2018):605-634.
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