Document Detail

Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells.
MedLine Citation:
PMID:  18057119     Owner:  NLM     Status:  MEDLINE    
In the renal cortex the peritubular capillary network and the proximal tubular epithelium cooperate in solute and water reabsorption, secretion, and inflammation. However, the mechanisms by which these two cell types coordinate such diverse functions remain to be characterized. Here we investigated the influence of microvascular endothelial cells on proximal tubule cells, using a filter-based, noncontact, close-proximity coculture of the human microvascular endothelial cell line HMEC-1 and the human proximal tubular epithelial cell line HK-2. With the use of DNA microarrays the transcriptomes of HK-2 cells cultured in mono- and coculture were compared. HK-2 cells in coculture exhibited a differential expression of 99 genes involved in pathways such as extracellular matrix (e.g., lysyl oxidase), cell-cell communication (e.g., IL-6 and IL-1 beta), and transport (e.g., GLUT3 and lipocalin 2). HK-2 cells also exhibited an enhanced paracellular gating function in coculture, which was dependent on HMEC-1-derived extracellular matrix. We identified a number of HMEC-1-enriched genes that are potential regulators of epithelial cell function such as extracellular matrix proteins (e.g., collagen I, III, IV, and V, laminin-alpha IV) and cytokines/growth factors (e.g., hepatocyte growth factor, endothelin-1, VEGF-C). This study demonstrates a complex network of communication between microvascular endothelial cells and proximal tubular epithelial cells that ultimately affects proximal tubular cell function. This coculture model and the data described will be important in the further elucidation of microvascular endothelial and proximal tubular epithelial cross talk mechanisms.
Sonia Aydin; Sara Signorelli; Thomas Lechleitner; Michael Joannidis; Clara Pleban; Paul Perco; Walter Pfaller; Paul Jennings
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-05
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  294     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-15     Completed Date:  2008-04-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C543-54     Citation Subset:  IM    
Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria.
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MeSH Terms
Capillaries / metabolism,  ultrastructure
Cell Communication / genetics*
Cell Line
Cell Line, Transformed
Cell Membrane Permeability / genetics
Coculture Techniques
Endothelium, Vascular / cytology,  metabolism*
Epithelial Cells / cytology,  metabolism*
Extracellular Matrix Proteins / genetics
Gene Expression Regulation / genetics
Intercellular Signaling Peptides and Proteins / genetics
Kidney / blood supply,  metabolism
Kidney Tubules, Proximal / cytology,  metabolism*
Oligonucleotide Array Sequence Analysis
Signal Transduction / genetics
Transcription, Genetic / genetics*
Up-Regulation / genetics
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Intercellular Signaling Peptides and Proteins

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