Linked Life Data

17999087

Source:http://linkedlifedata.com/resource/pubmed/id/17999087

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-11
pubmed:abstractText
In some capillary beds, pericytes regulate endothelial growth. Capillaries with high filtration capacity, such as those in renal glomeruli, lack pericytes. Glomerular endothelium lies adjacent to visceral epithelial cells (podocytes) that are anchored to and cover the anti-luminal surface of the basement membrane. We have tested the hypothesis that podocytes can function as endothelial supporting cells. Endothelial cells were outgrown from circulating endothelial progenitors of normal subjects and were extensively characterized. These blood outgrowth endothelial cells (BOECs) expressed endothelial markers, lacked stem cell markers, and expressed the angiopoietin-1 receptor, Tie-2, and the vascular endothelial growth factor (VEGF) receptor, Flk-1. Differentiated podocytes in culture expressed and secreted VEGF, which was upregulated 4.5-fold by high glucose. In complete medium, BOECs formed thin cell-cell connections and multicellular tubes on Matrigel, the in vitro correlate of angiogenesis. This was impaired in deficient media but rescued by co-incubation with Transwell Anopore inserts containing differentiated podocytes. To assess whether VEGF was the major podocyte-derived signal that rescued BOEC angiogenesis, we examined angiogenesis of control and Flk-1-deficient BOECs. Co-incubation with podocytes or addition of recombinant VEGF each rescued angiogenesis in control BOECs, but both failed to support maintenance and angiogenesis in Flk-1-deficient BOECs. Finally, co-culture with podocytes increased BOEC-proliferation. In concert, these findings suggest a model in which glomerular visceral epithelial cells function as pericyte-like endothelial supporting cells. Podocyte-derived VEGF is a required and sufficient regulator of vascular endothelial maintenance, and its upregulation in podocytes by high glucose may be the mechanism for the increased glomerular angiogenesis that is observed in vivo in early diabetic glomerular injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0302-766X
pubmed:author
pubmed:issnType
Print
pubmed:volume
331
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
485-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Functional symbiosis between endothelium and epithelial cells in glomeruli.
pubmed:affiliation
Los Angeles Biomedical Research Institute, 1124 West Carson Street, Torrance, CA 90502, USA. rhirschberg@labiomed.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural