Lopez-Anton, M, Lambie, MR, Lopez-Cabrera, M, Schmitt, CP, Ruiz-Carpio, V, Bartosova, M, Schaefer, B, Davies, SJ, Stone, T, Jenkins, R, Taylor, PR, Topley, N, Bowen, T and Fraser, D (2017) miR-21 Promotes Fibrogenesis in Peritoneal Dialysis. American Journal of Pathology, 187 (7). pp. 1537-1550. ISSN 1525-2191

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M Lambie - MicroRNA-21 promotes fibrogenesis in peritoneal dialysis.pdf - Accepted Version
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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.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://doi.org/10.1016/j.ajpath.2017.03.007 Please refer to any applicable terms of use of the publisher.
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine and Health Sciences > Institute for Applied Clinical Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 09 Jun 2017 14:38
Last Modified: 09 Jul 2018 15:19
URI: https://eprints.keele.ac.uk/id/eprint/3578

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