Genomic reprograming analysis of the Mesothelial to Mesenchymal Transition identifies biomarkers in peritoneal dialysis patients.
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.
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
Vicente
V
Ruiz-Carpio
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
Pilar
P
Sandoval
Unidad de Biología Molecular y Servicio de Nefrología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
Abelardo
A
Aguilera
Unidad de Biología Molecular y Servicio de Nefrología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
Patricia
P
Albar-Vizcaíno
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
María Luisa
ML
Perez-Lozano
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
Guadalupe T
GT
González-Mateo
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
Adrián
A
Acuña-Ruiz
Unidad de Genómica, CAI de Genómica y Proteómica, Universidad Complutense de Madrid, Madrid, Spain.
Jesús
J
García-Cantalejo
Unidad de Genómica, CAI de Genómica y Proteómica, Universidad Complutense de Madrid, Madrid, Spain.
Pedro
P
Botías
Servicio de Nefrología, Hospital Universitario La Paz, Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain.
María Auxiliadora
MA
Bajo
Servicio de Nefrología, Hospital Universitario La Paz, Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain.
Rafael
R
Selgas
Unidad de Biología Molecular y Servicio de Nefrología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
José Antonio
JA
Sánchez-Tomero
Fresenius Medical Care Deutschland GmbH, Else-Kröner-Straβe 1, 61352 Bad Homburg, Germany.
Jutta
J
Passlick-Deetjen
Fresenius Medical Care Deutschland GmbH, Else-Kröner-Straβe 1, 61352 Bad Homburg, Germany.
Dorothea
D
Piecha
Fresenius Medical Care Deutschland GmbH, Else-Kröner-Straβe 1, 61352 Bad Homburg, Germany.
Janine
J
Büchel
Fresenius Medical Care Deutschland GmbH, Else-Kröner-Straβe 1, 61352 Bad Homburg, Germany.
Sonja
S
Steppan
Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
Manuel
M
López-Cabrera
D015415:Biomarkers; D065150:Cellular Reprogramming / Q000235:genetics*; D015314:Dialysis Solutions / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods; D006019:Glycolysis; D006801:Humans; D010530:Peritoneal Dialysis / Q000009:adverse effects; D059467:Transcriptome
D015415:Biomarkers; D015314:Dialysis Solutions