Document Detail

Glucose modulates handling of apoptotic cells by mesangial cells: involvement of TGF-beta1.
MedLine Citation:
PMID:  17530031     Owner:  NLM     Status:  MEDLINE    
Glucose stimulates proapoptotic signalling pathways in mesangial cells. Studies focused on inflammatory glomerular injury have demonstrated that removal of apoptotic mesangial cells occurs by neighbouring non-apoptotic mesangial cells. The aim of this study was to define the effect of ambient glucose concentration on mesangial handling of apoptotic cells, and in addition to examine the response made by the mesangial cell. We used a co-culture model in which neutrophils aged overnight to induce apoptosis, or apoptotic mesangial cells, labelled with a fluorescent dye, were added to mesangial cells to study phagocytosis. Exposure of mesangial cells to an ambient glucose concentration of 25 mM D-glucose before addition of apoptotic cells led in an increase in mesangial cell phagocytosis. Ingestion of apoptotic cells was inhibited by blocking alpha v beta 3 integrin-vitronectin receptor or thrombospondin-1. Furthermore, glucose-dependent stimulation of phagocytosis was inhibited by a blocking antibody to TGF-beta1. Co-culture of apoptotic cells with mesangial cells stimulated synthesis of TGF-beta1 as compared to freshly isolated neutrophils. Increased TGF-beta1 synthesis was dependent on direct contact between the two cell types but was not dependent on phagocytosis of apoptotic cells, as TGF-beta1 generation was not affected by inhibition of the thrombospondin-1 pathway. We propose a model in which apoptotic cell binding but not phagocytosis stimulates enhanced mesangial cell TGF-beta1 synthesis. Furthermore phagocytosis, which involves the thrombospondin-1 pathway, is uncoupled from binding of apoptotic cells, which stimulated TGF-beta1 synthesis.
Tarnjit K Khera; John Martin; Stephen G Riley; Robert Steadman; Aled O Phillips
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-28
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  87     ISSN:  0023-6837     ISO Abbreviation:  Lab. Invest.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-14     Completed Date:  2007-09-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  690-701     Citation Subset:  IM    
Institute of Nephrology, School of Medicine, Cardiff University, Wales, UK.
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MeSH Terms
Apoptosis / physiology*
Cells, Cultured
Coculture Techniques
Dose-Response Relationship, Drug
Flow Cytometry
Fluorescent Dyes
Glucose / chemistry,  metabolism*
Integrin alphaVbeta3 / antagonists & inhibitors,  metabolism
Mesangial Cells / cytology,  metabolism*
Models, Biological
Neutrophils / physiology
Oligopeptides / chemistry,  metabolism
Phagocytosis / drug effects,  physiology
Signal Transduction
Thrombospondin 1 / metabolism
Transforming Growth Factor beta1 / biosynthesis*,  drug effects,  secretion
Reg. No./Substance:
0/Fluorescent Dyes; 0/Integrin alphaVbeta3; 0/Oligopeptides; 0/Thrombospondin 1; 0/Transforming Growth Factor beta1; 50-99-7/Glucose; 91037-65-9/arginyl-glycyl-aspartyl-serine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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