Document Detail


Overexpression of extracellular matrix proteins in renal tubulointerstitial cells by platelet-activating-factor stimulation.
MedLine Citation:
PMID:  9568845     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: One common feature of renal diseases is the development of interstitial fibrosis, but the mechanism of this process remains undefined. We hypothesized that platelet-activating factor (PAF), a classical acute inflammatory mediator involved in the pathogenesis of renal damage, acts on renal tubulointerstitial cells, contributing to the development of fibrosis. For this reason we evaluated the effect of PAF on matrix regulation and cell-growth-related events in tubulointerstitial cells. METHODS: In vitro studies were conducted with two tubulointerstitial cell lines: renal tubuloepithelial cells (NRK 52E) and interstitial fibroblasts (NRK 49F). The effect of PAF on extracellular matrix gene expression was determined by Northern blot. Fibronectin synthesis was quantified by metabolic labelling and immunoprecipitation. Cell growth changes were evaluated by fluorescence-activated cell-sorting analysis (cell cycle and size) and total protein content by 3[H]leucine incorporation. RESULTS: In renal tubuloepithelial cells and interstitial fibroblasts, PAF increased fibronectin mRNA expression. PAF-effect on the expression of collagen genes differed depending on the cell type studied. In tubuloepithelial cells there was an increase in type I and IV collagen mRNA levels, while only type I collagen was increased in fibroblasts. The overexpression of matrix proteins induced by PAF was completely blocked by preincubation of cells with the PAF receptor antagonist, BN52021. The PAF-induced upregulation of fibronectin expression was correlated with the increase in fibronectin synthesis. These effects were not associated with an increase in hyperplasia (characterized by changes in cell cycle) either in tubuloepithelial cells or in interstitial fibroblasts. Moreover, PAF did not induce tubular hypertrophy (changes in protein content and cell size). CONCLUSIONS: Our data suggest that PAF could be a mediator involved in extracellular matrix accumulation and, therefore, participate in the formation of renal interstitial fibrosis.
Authors:
M Ruiz-Ortega; C Bustos; J J Plaza; J Egido
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  13     ISSN:  0931-0509     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-06-11     Completed Date:  1998-06-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  886-92     Citation Subset:  IM    
Affiliation:
Renal Research Laboratory, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Size / drug effects
DNA / analysis
Epithelial Cells / drug effects
Extracellular Matrix Proteins / biosynthesis*,  genetics
Fibroblasts / drug effects
Fibrosis
Kidney Tubules / drug effects*,  metabolism,  pathology
Platelet Activating Factor / toxicity*
RNA, Messenger / analysis
Rats
Chemical
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Platelet Activating Factor; 0/RNA, Messenger; 9007-49-2/DNA

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


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