Identification of specific Tie2 cleavage sites and therapeutic modulation in experimental sepsis
Idowu TO, Etzrodt V, Seeliger B, Bolanos-Palmieri P, Thamm K, Haller H, David S (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 9
DOI: 10.7554/eLife.59520
Abstract
Endothelial Tie2 signaling plays a pivotal role in vascular barrier maintenance at baseline and after injury. We previously demonstrated that a sharp drop in Tie2 expression observed across various murine models of critical illnesses is associated with increased vascular permeability and mortality. Matrix metalloprotease (MMP)-14-mediated Tie2 ectodomain shedding has recently been recognized as a possible mechanism for Tie2 downregulation in sepsis. Here, we identified the exact MMP14-mediated Tie2 ectodomain cleavage sites and could show that pharmacological MMP14 blockade in experimental murine sepsis exerts barrier protective and anti-inflammatory effects predominantly through the attenuation of Tie2 cleavage to improve survival both in a pre-treatment and rescue approach. Overall, we show that protecting Tie2 shedding might offer a new therapeutic opportunity for the treatment of septic vascular leakage.
Additional Organisation(s)
Involved external institutions
Germany (DE)How to cite
APA:
Idowu, T.O., Etzrodt, V., Seeliger, B., Bolanos-Palmieri, P., Thamm, K., Haller, H., & David, S. (2020). Identification of specific Tie2 cleavage sites and therapeutic modulation in experimental sepsis. eLife, 9. https://dx.doi.org/10.7554/eLife.59520
MLA:
Idowu, Temitayo O., et al. "Identification of specific Tie2 cleavage sites and therapeutic modulation in experimental sepsis." eLife 9 (2020).
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