miR-21 Promotes Fibrogenesis in Peritoneal Dialysis.

Abstract

Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-β1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in peritoneal membrane biopsy specimens from PD patients compared to healthy controls (PD biocompatible, 5.86×, P = 0.0001; PD conventional, 7.09×, P < 0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21 was higher in those receiving the therapy long-term compared to new starters (n = 230, miR-21 3.26×, P = 0.001) and associated with icodextrin use (R = 0.52; 95% CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell death 4 protein was decreased in peritoneal membrane biopsy specimens from PD patients compared to healthy controls. New miR-21 targets were identified that may be important during PD fibrogenesis. These data identify miR-21 as an important effector of fibrosis in the peritoneal membrane, and a promising biomarker in the dialysis effluent for membrane change in patients receiving PD.

• Authors: Melisa Lopez-Anton, Mark Lambie, Manuel Lopez-Cabrera, Claus P Schmitt, Vicente Ruiz-Carpio, Maria Bartosova, Betti Schaefer, Simon Davies, Timothy Stone, Robert Jenkins, Philip R Taylor, Nicholas Topley, Timothy Bowen, Donald Fraser
• Journal: The American journal of pathology (Am J Pathol) Vol. 187 Issue 7 Pg. 1537-1550 (Jul 2017) ISSN: 1525-2191 [Electronic] United States
• PMID: 28495592 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Glucans
• MIRN21 microRNA, human
• MicroRNAs
• Icodextrin
• Glucose

Topics

• Biomarkers (analysis)
• Cells, Cultured
• Cohort Studies
• Down-Regulation
• Epithelial Cells (metabolism)
• Epithelium (metabolism)
• Gene Expression Regulation
• Glucans (therapeutic use)
• Glucose (therapeutic use)
• Humans
• Icodextrin
• Kidney Failure, Chronic (therapy)
• MicroRNAs (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Peritoneal Dialysis
• Peritoneal Fibrosis (genetics, metabolism)
• Peritoneum (metabolism)
• Peritonitis (genetics, metabolism)
• Treatment Failure
• Up-Regulation