0000000000805503
AUTHOR
Berend Isermann
Integrin Alphav-beta3 on Podocytes Orchestrates Coagulation Protease Signaling through Protease-Activated Receptors
Abstract Introduction Coagulation protease signaling via protease-activated receptors (PARs) is essential for maintenance of cellular homeostasis. Perturbed or aberrant activation of protease-dependent signaling via PARs propagates inflammation and pathological responses in disease models such as sepsis, neurological diseases and metabolic diseases including atherosclerosis, obesity and diabetic nephropathy (dNP). Disruption of protease-activated protein C (aPC) signaling in renal epithelial cells, i.e. podocytes, compromises adaptive endoplasmic reticulum (ER) signaling, promoting maladaptive ER-stress and ultimately dysfunction of the glomerular filtration barrier and dNP. While these res…
A20 expression in dendritic cells protects mice from LPS-induced mortality
DCs contribute to immune homeostasis under physiological conditions and regulate the immune activation during infection. The deubiquitinase A20 inhibits the activation of NF-κB-dependent immune reactions, and prevents the hyperactivation of DCs under steady-state conditions. However, the role of DC-specific A20 under pathological conditions is unknown. Here, we demonstrate that upon injection of low-dose LPS, mice with DC-specific A20 deletion (CD11c-Cre A20(fl/fl) ) died within 6 h, whereas A20(fl/fl) controls survived. LPS-induced mortality in CD11c-Cre A20(fl/fl) mice was characterized by increased serum levels of IL-2, IL-10, IL-12, IFN-γ, and TNF. Upon LPS stimulation, the activation o…
Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain—Brief Report
Objective: THBD (thrombomodulin) is part of the anticoagulant protein C-system that acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes. A recombinant soluble form of THBD was shown to have protective effects in different organs, but how the endogenous THBD is regulated during ischemia, particularly in the brain is not known to date. The aim of this study was to investigate the role of THBD, especially in brain endothelial cells, during ischemic stroke. Approach and Results: To induce ischemic brain damage, we occluded the middle cerebral artery of mice. We found an increased endothelial expression of Thbd in the peri-infarct area, whereas in the …