Shock-induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function

Both hemorrhagic shock and endotoxemia induce a pronounced vascular activation in the kidney which coincides with albuminuria and glomerular barrier dysfunction. We hypothesized that changes in Tie2, a vascular restricted receptor tyrosine kinase shown to control microvascular integrity and endothel...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Renal physiology 2009-08, Vol.297 (2), p.F272-F281
Main Authors: van Meurs, Matijs, Kurniati, Neng F, Wulfert, Francis M, Asgeirsdottir, Sigridur A, de Graaf, Inge A, Satchell, Simon C, Mathieson, Peter W, Jongman, Rianne M, Kümpers, Philipp, Zijlstra, Jan G, Heeringa, Peter, Molema, Grietje
Format: Article
Language:English
Subjects:
Aged
Albuminuria - metabolism
Albuminuria - physiopathology
Animals
Capillary Permeability
Cell culture
Cell Line
Disease Models, Animal
Down-Regulation
Endothelium, Vascular - metabolism
Endothelium, Vascular - physiopathology
Gene expression
Glomerular Filtration Rate
Humans
In Vitro Techniques
Kidney - blood supply
Kidney - metabolism
Kidney - physiopathology
Kidneys
Kinases
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
Microvessels - metabolism
Middle Aged
Neutrophils - metabolism
Physiology
Proteins
Receptor Protein-Tyrosine Kinases - genetics
Receptor Protein-Tyrosine Kinases - metabolism
Receptor, TIE-2 - genetics
Receptor, TIE-2 - metabolism
Ribonucleic acid
RNA
RNA, Messenger - metabolism
Rodents
Shock, Hemorrhagic - metabolism
Shock, Hemorrhagic - physiopathology
Shock, Septic - chemically induced
Shock, Septic - metabolism
Shock, Septic - physiopathology
Time Factors
Tumor Necrosis Factor-alpha - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Both hemorrhagic shock and endotoxemia induce a pronounced vascular activation in the kidney which coincides with albuminuria and glomerular barrier dysfunction. We hypothesized that changes in Tie2, a vascular restricted receptor tyrosine kinase shown to control microvascular integrity and endothelial inflammation, underlie this loss of glomerular barrier function. In healthy murine and human kidney, Tie2 is heterogeneously expressed in all microvascular beds, although to different extents. In mice subjected to hemorrhagic and septic shock, Tie2 mRNA and protein were rapidly, and temporarily, lost from the renal microvasculature, and normalized within 24 h after initiation of the shock insult. The loss of Tie2 protein could not be attributed to shedding as both in mice and healthy volunteers subjected to endotoxemia, sTie2 levels in the systemic circulation did not change. In an attempt to identify the molecular control of Tie2, we activated glomerular endothelial cell cultures and human kidney slices in vitro with LPS or TNF-alpha, but did not observe a change in Tie2 mRNA levels. In parallel to the loss of Tie2 in vivo, an overt influx of neutrophils in the glomerular compartment, which coincided with proteinuria, was seen. As neutrophil-endothelial cell interactions may play a role in endothelial adaptation to shock, and these effects cannot be mimicked in vitro, we depleted neutrophils before shock induction. While this neutrophil depletion abolished proteinuria, Tie2 was not rescued, implying that Tie2 may not be a major factor controlling maintenance of the glomerular filtration barrier in this model.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00137.2009