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Sci Rep. 2017 Mar 22;7:44941. doi: 10.1038/srep44941.

Genomic reprograming analysis of the Mesothelial to Mesenchymal Transition identifies biomarkers in peritoneal dialysis patients.

Author information

1
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
2
Unidad de Biología Molecular y Servicio de Nefrología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
3
Unidad de Genómica, CAI de Genómica y Proteómica, Universidad Complutense de Madrid, Madrid, Spain.
4
Servicio de Nefrología, Hospital Universitario La Paz, Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain.
5
Fresenius Medical Care Deutschland GmbH, Else-Kröner-Straβe 1, 61352 Bad Homburg, Germany.

Abstract

Peritoneal dialysis (PD) is an effective renal replacement therapy, but a significant proportion of patients suffer PD-related complications, which limit the treatment duration. Mesothelial-to-mesenchymal transition (MMT) contributes to the PD-related peritoneal dysfunction. We analyzed the genetic reprograming of MMT to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping between MMT induced in vitro and ex vivo in effluent-derived mesothelial cells, and that MMT is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. Cellular morphology and number of altered genes showed that MMT ex vivo could be subdivided into two stages: early/epithelioid and advanced/non-epithelioid. RT-PCR array analysis demonstrated that a number of genes differentially expressed in effluent-derived non-epithelioid cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were measured in PD effluents, and except GREM1, showed significant differences between early and advanced stages of MMT, and their expression was associated with a high peritoneal transport status. The results establish a proof of concept about the feasibility of measuring MMT-associated secreted protein levels as potential biomarkers in PD.

PMID:
28327551
PMCID:
PMC5361179
DOI:
10.1038/srep44941
[Indexed for MEDLINE]
Free PMC Article

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