Circulating long noncoding rna lnc-epha6 associates with acute rejection after kidney transplantation

Koen E. Groeneweg, Jacques M.G.J. Duijs, Barend W. Florijn, Cees van Kooten, Johan W. de Fijter, Anton Jan van Zonneveld, Marlies E.J. Reinders, Roel Bijkerk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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Abstract

Acute rejection (AR) of a kidney graft in renal transplant recipients is associated with microvascular injury in graft dysfunction and, ultimately, graft failure. Circulating long noncoding RNAs (lncRNAs) may be suitable markers for vascular injury in the context of AR. Here, we first investigated the effect of AR after kidney transplantation on local vascular integrity and demonstrated that the capillary density markedly decreased in AR kidney biopsies compared to pre-transplant biopsies. Subsequently, we assessed the circulating levels of four lncRNAs (LNC-RPS24, LNC-EPHA6, MALAT1, and LIPCAR), that were previously demonstrated to associate with vascular injury in a cohort of kidney recipients with a stable kidney transplant function (n = 32) and recipients with AR (n = 15). The latter were followed longitudinally six and 12 months after rejection. We found higher levels of circulating LNC-EPHA6 during rejection, compared with renal recipients with a stable kidney function (p = 0.017), that normalized one year after AR. In addition, LNC-RPS24, LNC-EPHA6, and LIPCAR levels correlated significantly with the vascular injury marker soluble thrombomodulin. We conclude that AR and microvascular injury are associated with higher levels of circulating LNC-EPHA6, which emphasizes the potential role of lncRNAs as biomarker in the context of AR.

Original languageEnglish
Article number5616
Pages (from-to)1-9
Number of pages9
JournalInternational Journal of Molecular Sciences
Volume21
Issue number16
DOIs
Publication statusPublished - 5 Aug 2020
Externally publishedYes

Bibliographical note

Funding:
This research was supported by a grant from the Dutch Kidney Foundation (grant number 16OKG16). R.B. and A.J.v.Z. are supported by a grant from the European Foundation for the Study of Diabetes (EFSD).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

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