Monocyte- and Endothelial-Derived Microparticles Induce an Inflammatory Phenotype in Human Podocytes

J Eyre, JO Burton, MA Saleem, PW Mathieson, PS Topham, NJ Brunskill

Research output: Contribution to journalArticle (Academic Journal)peer-review

33 Citations (Scopus)

Abstract

Background/Aims: Proteinuria is associated with cardiovascular and chronic kidney disease. Microparticles (MPs) are bioactive vesicles shed from activated cells and also linked to cardiovascular disease. MP-like structures have been identified in the glomerular basement membrane, urinary space and between the glomerular basement membrane and the podocyte. We hypothesised that circulating MPs may provide a link between vascular injury and kidney diseases by inducing podocyte phenotypic alterations, thus propagating glomerular dysfunction and proteinuria. Methods:Human umbilical vein endothelial cells and U937 monocytes were stimulated with TNF-α to produce MPs. These MPs were confirmed by electron microscopy, and added to differentiated podocyte monolayers to determine effects on podocyte albumin endocytosis and the production of soluble mediators. Results:Monocyte and endothelial MPs upregulated podocyte production of pro-inflammatory mediators monocyte chemoattractant protein-1 (p <0.001) and interleukin-6 (p <0.001). Only monocyte MPs upregulated podocyte secretion of VEGF (p <0.001), known to regulate glomerular permeability. Endothelial MPs decreased podocyte albumin endocytosis by 13% compared to control cells (p <0.01). Conclusion:MPs alter endocytic functions of podocytes and induce secretion of pro-inflammatory cytokines, potentially leading to glomerular inflammation in vivo and the development of proteinuria. This study identifies a potential pathophysiological role for circulating MPs in the kidney through effects on the podocyte.
Translated title of the contributionMonocyte- and Endothelial-Derived Microparticles Induce an Inflammatory Phenotype in Human Podocytes
Original languageEnglish
Pages (from-to)e58 - e66
Number of pages11
JournalNephron Experimental Nephrology
Volume18;119(3)
DOIs
Publication statusPublished - Aug 2011

Fingerprint Dive into the research topics of 'Monocyte- and Endothelial-Derived Microparticles Induce an Inflammatory Phenotype in Human Podocytes'. Together they form a unique fingerprint.

Cite this