Diabetic nephropathy alters circulating long noncoding RNA levels that normalize following simultaneous pancreas–kidney transplantation
American Journal of Transplantation, vol. 20, pp. 3451–3461
Abstract
Simultaneous pancreas–kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with diabetic nephropathy (DN). Here, we aimed to identify circulating long noncoding RNAs (lncRNAs) that are associated with DN and vascular injury in the context of SPKT. Based on a pilot study and a literature-based selection of vascular injury–related lncRNAs, we assessed 9 candidate lncRNAs in plasma samples of patients with diabetes mellitus with a kidney function >35 mL/min/1.73 m2 (DM; n = 12), DN (n = 14), SPKT (n = 35), healthy controls (n = 15), and renal transplant recipients (KTx; n = 13). DN patients were also studied longitudinally before and 1, 6, and 12 months after SPKT. Of 9 selected lncRNAs, we found MALAT1, LIPCAR, and LNC-EPHA6 to be higher in DN compared with healthy controls. SPKT caused MALAT1, LIPCAR, and LNC-EPHA6 to normalize to levels of healthy controls, which was confirmed in the longitudinal study. In addition, we observed a strong association between MALAT1, LNC-EPHA6, and LIPCAR and vascular injury marker soluble thrombomodulin and a subset of angiogenic microRNAs (miR-27a, miR-130b, miR-152, and miR-340). We conclude that specific circulating lncRNAs associate with DN-related vascular injury and normalize after SPKT, suggesting that lncRNAs may provide a promising novel monitoring strategy for vascular integrity in the context of SPKT.
Authors 9
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Koen E. Groeneweg Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Yu Wah Au Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Jacques M.G.J. Duijs Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Barend W. Florijn Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Cees van Kooten Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Johan Willem de Fijter Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Marlies E. J. Reinders Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Anton Jan van Zonneveld Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Roel Bijkerk corresponding Aachen Department of Internal Medicine Einthoven Laboratory for Vascular and Regenerative Medicine
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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