Transcriptional Perturbations in Graft Rejection. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Vitalone, Matthew J.; Sigdel, Tara K.; Salomonis, Nathan; Sarwal, Reuben D.; Hsieh, Szu-Chuan; Sarwal, Minnie M.
• Is Part Of: Transplantation. Volume 99:Issue 9(2015)
• Publication Date: 2015-09
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000809
• Languages: English
• ISSNs: 0041-1337

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>Understanding the regulatory interplay of relevant microRNAs (miRNAs) and messenger RNAs (mRNAs) in the rejecting allograft will result in a better understanding of the molecular pathophysiology of alloimmune injury.</p> </sec> <sec> <title>Methods</title> <p>One hundred sixty-seven allograft biopsies, with (n = 47) and without (n = 120) central histology for Banff scored acute rejection (AR), were transcriptionally profiled for mRNA and miRNA by whole genome microarrays and multiplexed microfluidic quantitative polymerase chain reaction, respectively. A customized database was curated (GO-Elite) and used to identify AR-specific dysregulated mRNAs and the role of perturbations of their relevant miRNAs targets during AR.</p> </sec> <sec> <title>Results</title> <p>The AR-specific changes in 1035 specific mRNAs were mirrored by AR-specific perturbations in 9 relevant miRNAs as predicted by Go-Elite and were regulated specifically by p53 and forkhead box P3. Infiltrating lymphocytes and the renal tubules drove the miRNA tissue pertubations in rejection, involving message degradation and transcriptional/translational activation. The expression of many of these miRNAs significantly associated with the intensity of the Banff-scored interstitial inflammation and tubulitis.</p> </sec> <sec> <title>Conclusions</title> <p>There is a highly regulated interplay between specific mRNA/miRNAs in allograft rejection that drive both immune-mediated injury and tissue repair during AR.</p> </sec> </abstract>