期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 187, 期 7, 页码 1537-1550出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2017.03.007
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资金
- Marie Curie Innovative Training Network grant, European Training and Research in Peritoneal Dialysis [287813]
- Wellcome Trust [107964/Z/15/Z] Funding Source: Wellcome Trust
- MRC [MR/K02003X/1] Funding Source: UKRI
- Kidney Research UK [PDF6/2013] Funding Source: researchfish
- Medical Research Council [MR/K02003X/1] Funding Source: researchfish
- Wellcome Trust [107964/Z/15/Z] Funding Source: researchfish
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-beta 1 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, 5.86x, 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 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.
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