Journal
EUROPEAN JOURNAL OF CELL BIOLOGY
Volume 96, Issue 4, Pages 289-300Publisher
ELSEVIER GMBH
DOI: 10.1016/j.ejcb.2017.04.002
Keywords
Microvascular endothelial cells; Endothelial to mesenchymal transition; Migration; Matrix metalloproteinases; Podosomes
Categories
Funding
- Polish-Norwegian Research Program [Pol-Nor/202952/5/2013]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available