Skip to main content
Fig. 12 | Particle and Fibre Toxicology

Fig. 12

From: Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation

Fig. 12

Proposed signaling pathway(s) responsible for SiNPs-induced endothelial barrier injury based on the present study and published literatures. In brief, SiNPs activate CRAC channels at the extracellular side and lead to Ca2+ influx (endocytosed SiNPs might also affect the CRAC channel and other proteins from the intracellular side); Ca2+ influx induces Ca2+ release from the endoplasmic reticulum (ER) via a Ca2+-induced Ca2+ release (CICR) mechanism; Ca2+ influx and Ca2+ release lead to [Ca2+]i elevation; elevated [Ca2+]i activates calpain and convert xanthine dehydrogenase (XD) to xanthine oxidase (XO), and XO catalyzes ROS generation; ROS mediates activation of Src family kinase, and activated Src induces VE-cadherin phosphorylation at the Y731 site and leads to VE-cadherin internalization and degradation and F-actin re-assembly, and finally leads to failure of endothelial barrier. Subsequent macrophage infiltration occurs across the inter-endothelial gap due to the injury. In this signaling chain, MY58483 inhibits CRAC channels and PP1 suppresses Src, and thus together ameliorate SiNPs-induced endothelial barrier injury. In addition, the endothelial toxicity of SiNPs may also lead to endothelial death/exfoliation and collagen exposure, thus trigger the contact pathway of coagulation in the blood vessels (not shown)

Back to article page