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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Albumin-induced epithelial mesenchymal transformation
Nephron - Experimental Nephrology, Volume 120, No. 3, Year 2012
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Description
Background: Progressive chronic kidney disease is often associated with albuminuria and renal fibrosis linked to the accumulation of myofibroblasts producing extracellular matrix. Renal myofibroblasts are derived from a number of cells including tubular epithelial cells (TECs) through epithelial mesenchymal transformation (EMT). This study explores the hypothesis that exposure of TECs to albumin induces EMT. Methods: Normal rat TECs (NRK52E) were exposed in culture to de-lipidated bovine serum albumin (dBSA; 10 mg/ml) for 2, 4 and 6 days. Binding/uptake of fluoresceined albumin by PTCs was evaluated. Transformation into myofibroblasts was assessed by light and electron microscopy, immunofluorescence and Western blotting for α-smooth muscle actin (α-SMA), E-cadherin and transforming growth factor-β1 (TGF-β1). We also investigated the expression of fibroblast-specific protein-1 (FSP-1) and collagens I, III and IV. TGF-β1 biological activity, mRNA and protein were measured. A neutralising anti-TGF-β1 antibody was used to analyse the role of TGF-β1 in albumin-induced EMT. Results: Exposure of TECs to dBSA led to binding/uptake of albumin as well as fibroblastic morphological changes. Incubation of TECs with dBSA caused a reduction of TEC marker E-cadherin (ANOVA p = 0.0002) and de novo expression of fibroblast markers α-SMA and FSP-1 (ANOVA p = 0.0001) in a time-dependent manner. It also increased expression and activity of TGF-β1. Neutralisation of TGF-β1 significantly reduced EMT (p < 0.01). Conclusion: This study demonstrates that in vitro, albumin induces the transformation of TECs into cells with myofibroblast characteristics; a process that may be TGF-β1 dependent. Copyright © 2012 S. Karger AG, Basel.
Authors & Co-Authors
Ibrini, J.
United Kingdom, Sheffield
The University of Sheffield
Fadel, Sanaa
United Kingdom, Sheffield
The University of Sheffield
Egypt, Giza
Cairo University
Chana, R. S.
United Kingdom, Leicester
University of Leicester
Brunskill, N. J.
United Kingdom, Leicester
University of Leicester
Wagner, B.
United Kingdom, Sheffield
The University of Sheffield
Johnson, Timothy S.
United Kingdom, Sheffield
The University of Sheffield
El-Nahas, Abdel Meguid
United Kingdom, Sheffield
The University of Sheffield
United Kingdom, Sheffield
Northern General Hospital
Statistics
Citations: 22
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1159/000336822
e-ISSN:
16602129
Research Areas
Noncommunicable Diseases