TNF ROCK s the boat as the kidney endothelium springs a leak

Abnormal vascular permeability is a hallmark of sepsis‐mediated injury to various organs. An intact endothelial barrier is critical to homeostasis and prevents leakage of abnormal quantities of fluid and protein, including proinflammatory cytokines and chemokines, into the extravascular space. Barrier disruption leads to distributive shock as well as organ dysfunction and edema (Lee and Slutsky 2010).Extensive research implicates tumor necrosis factor‐ α (TNF) in this process. TNF binds receptors on the endothelial cell surface and activates intracellular Rho GTPases. This increases Rho‐associated kinase (ROCK) activity which inactivates myosin light chain (MLC) phosphatase and, in the presence of myosin light chain kinase (MLCK), leads to MLC phosphorylation. As a result, actin filaments reorganize into stress fibers, and cells exhibit increased actomyosin contractility, leading to endothelial barrier disruption (Marcos‐Ramiro et al. 2014).Endothelial permeability in the kidney has unique manifestations. Similar to other organs, dysfunction of endothelia in the peritubular capillaries leads to reduced blood flow and inflammation that contribute to AKI pathogenesis (Molitoris 2014). In addition, the specialized glomerular endothelium, together with the glomerular epithelium (i.e., podocytes) and associated basement membrane, forms the kidney's filtration barrier. Disruption of the filtration barrier leads to proteinuria, or the abnormal accumulation of protein in the …