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NDT Advance Access originally published online on July 22, 2006
Nephrology Dialysis Transplantation 2006 21(10):2943-2947; doi:10.1093/ndt/gfl355
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Ex vivo reversal of in vivo transdifferentiation in mesothelial cells grown from peritoneal dialysate effluents

Regina Vargha, Michaela Endemann, Klaus Kratochwill, Andrea Riesenhuber, Nikolaus Wick, Anne-Marie Krachler, Laura Malaga-Dieguez and Christoph Aufricht

Kinderdialyse, Department of Pediatrics, AKH Vienna, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria

Correspondence and offprint requests to: Prof. Dr Christoph Aufricht, Kinderdialyse, Department of Pediatrics, AKH Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Email: christoph.aufricht{at}meduniwien.ac.at

Background. During peritoneal dialysis (PD), epithelial–mesenchymal transition (EMT) is likely involved in aberrant healing and progressive peritoneal fibrosis. Recently, EMT of the kidney was actively reversed into the opposite direction, into mesenchymal–epithelial transition (MET), by treatment with bone morphogenic protein-7 (BMP-7). In this study, the potential for ex vivo interconversion of in vivo transdifferentiation processes was investigated in mesothelial cells.

Methods. In vivo EMT was assessed in mesothelial cell cultures randomly grown from peritoneal effluents of seven patients on chronic PD. Then, ex vivo treatment with modulating factors was performed by incubating cobblestone-like cell cultures with transforming growth factor (TGF- ß1) and fibroblast-like cultures with BMP-7. Effects were assessed by morphological characterization, western analysis and reverse transcription–polymerase chain reaction of marker proteins ezrin and {alpha}-smooth muscle actin ({alpha}-SMA).

Results. PD caused progressive in vivo EMT with loss of the epithelial phenotype in the majority of mesothelial cell cultures over a 12-month period. EMT was reproducible by ex vivo treatment of cultured cells with TGF-ß1, converting the epithelial to the fibroblast-like phenotype. Ex vivo treatment with BMP-7 reversed in vivo and ex vivo EMT. During rhBMP-7 incubation the fibroblast-like growth pattern reversed into a more epithelial morphology, the expression of ezrin increased and {alpha}-SMA decreased.

Conclusion. Our study shows that modulating factors of transdifferentiation, such as BMP-7, may be attractive tools in the balance between normal healing and aberrant profibrotic processes in mesothelial cells during peritoneal dialysis. Peritoneal-effluent-derived mesothelial cells are not mere biomarkers for in vivo EMT in the peritoneal cavity, but also represent an assay to test ex vivo interventions to reverse the profibrotic phenotype.

Keywords: BMP-7; epithelial–mesenchymal transition; mesenchymal–epithelial transition; mesothelial cells; peritoneal dialysis; peritoneal effluent; TGF-ß1


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