Regulation of endothelial migration and proliferation by ephrin-A1

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Endothelial migration and proliferation are fundamental processes in angiogenesis and wound healing of injured or inflamed vessels. The present study aimed to investigate the regulation of the Eph/ephrin-system during endothelial proliferation and the impact of the ligand ephrin-A1 on proliferation and migration of human umbilical venous (HUVEC) and arterial endothelial cells (HUAEC). Endothelial cells that underwent contact inhibition showed a massive induction of ephrin-A1. In contrast, an injury to a confluent endothelial layer, associated with induction of migration and proliferation, showed reduced ephrin-A1 levels. In addition, reducing ephrin-A1 expression by siRNA led to increased proliferation, whereas the overexpression of ephrin-A1 led to decreased proliferative activity. Due to the fact that wound healing is a combination of proliferation and migration, migration was investigated in detail. First, classical wound-healing assays showed increased wound closure in both ephrin-A1 silenced and overexpressing cells. Live-cell imaging enlightened the underlying differences. Silencing of ephrin-A1 led to a faster but more disorientated migration. In contrast, ephrin-A1 overexpression did not influence velocity of the cells, but the migration was more directed in comparison to the controls. Additional analysis of EphA2-silenced cells showed similar results in terms of proliferation and migration compared to ephrin-A1 silenced cells. Detailed analysis of EphA2 phosphorylation on ligand-dependent phospho-site (Y588) and autonomous activation site (S897) revealed a distinct phosphorylation pattern. Furthermore, the endothelial cells ceased to migrate when they came in contact with an ephrin-A1 coated surface. Using a baculoviral-mediated expression system, ephrin-A1 silencing and overexpression was shown to modulate the formation of focal adhesions. This implicates that ephrin-A1 is involved in changes of the actin cytoskeleton which explains the alterations in migratory actions, at least in part. In conclusion, ephrin-A1 expression is regulated by cellular density and is itself a critical determinant of endothelial proliferation. According to current knowledge, ephrin-A1 seems to be remarkably involved in elementary processes of endothelial migration like cellular polarization, migratory direction and speed. These data support the notion that ephrin-A1 plays a pivotal role in basal mechanisms of re-endothelialization.

Details

OriginalspracheEnglisch
Seiten (von - bis)84-95
Seitenumfang12
FachzeitschriftCellular Signalling
Jahrgang29
PublikationsstatusVeröffentlicht - 1 Jan. 2017
Peer-Review-StatusJa

Externe IDs

researchoutputwizard legacy.publication#78232
Scopus 84992650333
PubMed 27742560
ORCID /0000-0001-7803-1972/work/142235118

Schlagworte

Schlagwörter

  • Endothelial cells, In-stent-restenosis, Migration, Proliferation