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Published on: July 19, 2018
Genomic reprograming analysis of the Mesothelial to Mesenchymal Transition identifies biomarkers in peritoneal
Vicente Ruiz-Carpio1, Pilar Sandoval1, Abelardo Aguilera2
1Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Cantoblanco, Madrid, Spain.
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.
Insights
Mesothelial-to-mesenchymal transition (MMT) drives peritoneal dialysis complications. Researchers identified key protein biomarkers in patient fluid, offering potential for early detection and improved treatment monitoring in dialysis patients.
Area of Science:
- Nephrology
- Cell Biology
- Biomarker Discovery
Background:
- Peritoneal dialysis (PD) is a vital renal replacement therapy.
- PD-related complications, often linked to mesothelial-to-mesenchymal transition (MMT), limit treatment longevity.
- Identifying biomarkers for MMT is crucial for managing PD complications.
Purpose of the Study:
- To analyze the genetic reprogramming of MMT in peritoneal dysfunction.
- To identify potential biomarkers for MMT in patients undergoing peritoneal dialysis.
- To investigate the relationship between MMT stages and PD fluid composition.
Main Methods:
- Microarray analysis of MMT induced in vitro and ex vivo.
- RT-PCR array analysis of effluent-derived mesothelial cells.
- Quantification of specific proteins (TSP1, COL13, VEGFA, GREM1) in PD effluents.
Main Results:
- MMT involves significant gene repression, with distinct early (epithelioid) and advanced (non-epithelioid) stages observed ex vivo.
- Differential gene expression in advanced MMT correlated with PD fluid composition (standard vs. low-GDP).
- TSP1, COL13, and VEGFA levels differed between MMT stages and correlated with high peritoneal transport.
Conclusions:
- MMT is a complex genetic reprogramming process contributing to peritoneal dysfunction in PD.
- Specific proteins like TSP1, COL13, and VEGFA show promise as biomarkers for MMT stages and peritoneal transport status.
- Measuring MMT-associated secreted proteins in PD effluents is feasible and could aid in patient management.
