Endothelial Microparticles Delivering Lncrna NEAT1 Are Involved in the Pathophysiology of aGVHD Following Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Endothelial microparticles (EMPs) upregulation has been observed in the pathological process of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) carried by EMPs in aGVHD after allo-HSCT are still open questions. Herein, we investigated the functional significance of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) delivered by EMPs in aGVHD. To address this question, in the present study, we performed a comprehensive analysis of the lncRNA NEAT1 expression and EMPs in aGVHD by a series of in vivo and in vitro experiments. We found that expressions of lncRNA NEAT1 in MPs were remarkably elevated in aGVHD mice than in non-aGVHD mice. Furthermore, the lncRNA NEAT1 levels in the MPs were remarkably higher than those in the plasma of the aGVHD mice. We then used TNF-α (100 ng/ml) to stimulate primary mouse aortic endothelial cells (MAECs) to shed EMPs, and the expression of lncRNA NEAT1 in the EMPs and their maternal cells was compared. The lncRNA NEAT1 levels in the EMPs produced by TNF-α-stimulated MAECs were significantly higher than that in both their maternal cells and non-stimulated EMPs. Our study demonstrates that EMPs could assemble and concentrate lncRNA NEAT1. Taken together, NEAT1 delivered by EMPs could be used as a diagnostic and prognostic surrogate marker for aGVHD, and its targeting could therefore represent a promising strategy for novel therapeutic options in life-threatening aGVHD after allo-HSCT. Disclosures No relevant conflicts of interest to declare.