Piacvezérelt kutatás-fejlesztési és innovációs projektek támogatása(2020-1.1.2-PIACI-KFI-2021-00273)
Funder: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal
Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015)
Funder: NRDIO
(TKP2021-EGA-24)
Endothelial wound-healing processes are fundamental for the maintenance and restoration
of the circulatory system and are greatly affected by the factors present in the blood.
We have previously shown that the complement protein mannan-binding lectin-associated
serine protease-1 (MASP-1) induces the proinflammatory activation of endothelial cells
and is able to cooperate with other proinflammatory activators. Our aim was to investigate
the combined effect of mechanical wounding and MASP-1 on endothelial cells. Transcriptomic
analysis showed that MASP-1 alters the expression of wound-healing-related and angiogenesis-related
genes. Both wounding and MASP-1 induced Ca2+ mobilization when applied individually.
However, MASP-1-induced Ca2+ mobilization was inhibited when the treatment was preceded
by wounding. Mechanical wounding promoted CREB phosphorylation, and the presence of
MASP-1 enhanced this effect. Wounding induced ICAM-1 and VCAM-1 expression on endothelial
cells, and MASP-1 pretreatment further increased VCAM-1 levels. MASP-1 played a role
in the subsequent stages of angiogenesis, facilitating the breakdown of the endothelial
capillary network on Matrigel®. Our findings extend our general understanding of endothelial
wound healing and highlight the importance of complement MASP-1 activation in wound-healing
processes.