Journal
NATURE REVIEWS NEPHROLOGY
Volume 18, Issue 2, Pages 95-112Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41581-021-00489-1
Keywords
-
Categories
Ask authors/readers for more resources
Endothelial cells in the kidney microvasculature show intrinsic molecular and phenotypic heterogeneity, responding to sepsis-induced acute kidney injury in a segment-specific manner. They have been overlooked in sepsis-induced AKI research, although they have potential as pharmacological targets. Various molecular mechanisms control endothelial functions in the development of sepsis-induced AKI, with distinct responses in different microvascular segments.
Endothelial cells in the kidney microvasculature have an intrinsic molecular and phenotypic heterogeneity and respond to sepsis-induced acute kidney injury conditions in a segment-specific manner. This Review discusses the roles of these cells and the molecular systems that control endothelial functions in the development of sepsis-induced acute kidney injury. Microvascular endothelial cells in the kidney have been a neglected cell type in sepsis-induced acute kidney injury (sepsis-AKI) research; yet, they offer tremendous potential as pharmacological targets. As endothelial cells in distinct cortical microvascular segments are highly heterogeneous, this Review focuses on endothelial cells in their anatomical niche. In animal models of sepsis-AKI, reduced glomerular blood flow has been attributed to inhibition of endothelial nitric oxide synthase activation in arterioles and glomeruli, whereas decreased cortex peritubular capillary perfusion is associated with epithelial redox stress. Elevated systemic levels of vascular endothelial growth factor, reduced levels of circulating sphingosine 1-phosphate and loss of components of the glycocalyx from glomerular endothelial cells lead to increased microvascular permeability. Although coagulation disbalance occurs in all microvascular segments, the molecules involved differ between segments. Induction of the expression of adhesion molecules and leukocyte recruitment also occurs in a heterogeneous manner. Evidence of similar endothelial cell responses has been found in kidney and blood samples from patients with sepsis. Comprehensive studies are needed to investigate the relationships between segment-specific changes in the microvasculature and kidney function loss in sepsis-AKI. The application of omics technologies to kidney tissues from animals and patients will be key in identifying these relationships and in developing novel therapeutics for sepsis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available