期刊
EUROPEAN JOURNAL OF CELL BIOLOGY
卷 96, 期 4, 页码 289-300出版社
ELSEVIER GMBH
DOI: 10.1016/j.ejcb.2017.04.002
关键词
Microvascular endothelial cells; Endothelial to mesenchymal transition; Migration; Matrix metalloproteinases; Podosomes
类别
资金
- Polish-Norwegian Research Program [Pol-Nor/202952/5/2013]
The contribution of endothelial cells to scar and fibrotic tissue formation is undisputedly connected to their ability to undergo the endothelial-to-mesenchymal transition (EndMT) towards fibroblast phenotype-resembling cells. The migration model of fibroblasts and fibroblast-resembling cells is still not fully understood. It may be either a Rho/ROCK-independent, an integrin- and MMP-correlated ECM degradation-dependent, a mesenchymal model or Rho/ROCK-dependent, integrin adhesion- and MMP activity-independent, an amoeboid model. Here, we hypothesized that microvascular endothelial cells (HMEC-1) undergoing EndMT adopt an intermediate state of drifting migration model between the mesenchymal and amoeboid protrusive types in the early stages of fibrosis. We characterized the response of HMEC-1 to TGF-beta 2, a well-known mediator of EndMT within the microvasculature. We observed that TGF-beta 2 induces up to an intermediate mesenchymal phenotype in HMEC-1. In parallel, MMP-2 is upregulated and is responsible for most proteolytic activity. Interestingly, the migration of HMEC-1 undergoing EndMT is dependent on both ECM degradation and invadosome formation associated with MMP-2 proteolytic activity and Rho/ROCK cytoskeleton contraction. In conclusion, the transition from mesenchymal towards amoeboid movement highlights a molecular plasticity mechanism in endothelial cell migration in skin fibrosis. (C) 2017 Elsevier GmbH. All rights reserved.
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