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Mesenchymal Transition in Human Mesothelial Cells In Vitro and Ex Vivo

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE92455 | GEO | 2017/03/22

SECONDARY ACCESSION(S): PRJNA357605

REPOSITORIES: GEO

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Project description:Peritoneal dialysis (PD) is an effective form of renal replacement therapy. A significant proportion of patients who initiate PD suffer from PD-related clinical complications, including peritoneal membrane damage, which may limit the duration of treatment. Mesothelial-to-mesenchymal transition (MMT) significantly contributes to the peritoneal dysfunction related to PD. Hence, we analyzed the genetic reprograming of the MMT-process with the aim to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping of MMT induced in vitro and MMT of effluent-derived mesothelial cells (ex vivo), and that MMT, both in vitro and ex vivo, is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. According to cellular morphology and the number of altered genes and pathways, the MMT ex vivo could be subdivided into two stages: early/epitheliod and advanced/non-epitheliod. We could demonstrate by RT-PCR array analysis that a number of genes differentially expressed in effluent-derived non-epitheliod cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Among the secreted proteins that are up-regulated along the MMT process thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were selected to be measured in PD effluents. TSP1, COL13 and VEGFA, but not GREM1, showed significant differences between early and advanced stages of MMT, and their expression were associated with high peritoneal transport status. The results establish a proof of concept about the feasibility of MMT-associated secreted proteins as biomarkers in PD.

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