miR-21 promotes fibrogenesis in peritoneal dialysis

Lopez-Anton, Melisa, Lambie, Mark, Lopez-Cabrera, Manuel, Schmitt, Claus P., Ruiz-Carpio, Vicente, Bartosova, Maria, Schaefer, Betti, Davies, Simon, Stone, Timothy ORCID: https://orcid.org/0000-0003-4591-9611, Jenkins, Robert ORCID: https://orcid.org/0000-0001-8500-9044, Taylor, Philip R. ORCID: https://orcid.org/0000-0003-0163-1421, Topley, Nicholas, Bowen, Timothy ORCID: https://orcid.org/0000-0001-6050-0435 and Fraser, Donald ORCID: https://orcid.org/0000-0003-0102-9342 2017. miR-21 promotes fibrogenesis in peritoneal dialysis. American Journal of Pathology 187 (7) , pp. 1537-1550. 10.1016/j.ajpath.2017.03.007

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Abstract

Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with End Stage Kidney Disease. Mesothelial Cells (MC) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. MicroRNAs (miRNAs) are important regulators but their roles in peritoneal fibrosis are largely unknown. In this study microRNA-21 (miR-21) was one of the most abundant miRNAs in primary MCs, and was up regulated by the profibrotic cytokine TGF-β1 and in PD effluentderived MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in peritoneal membrane biopsies from PD patients compared to healthy controls (PD biocompatible, 5.86x, p=0.0001; PD conventional, 7.09x, 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 3.26x, p=0.001) and associated with Icodextrin usage R=0.52, (0.20, 0.84), peritonitis count R=0.16, (0.03, 0.29) and dialysate cytokines. MiR-21 down-regulated Programmed Cell Death 4 (PDCD4) and PDCD4 protein was decreased in peritoneal membrane biopsies from PD patients compared to healthy controls. New miR-21 targets were identified that may be important during peritoneal dialysis 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
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Elsevier
ISSN:	0002-9440
Date of First Compliant Deposit:	2 June 2017
Date of Acceptance:	28 March 2017
Last Modified:	24 Nov 2024 18:45
URI:	https://orca.cardiff.ac.uk/id/eprint/101064

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