Please use this identifier to cite or link to this item:
|Title:||Intragraft antiviral-specific gene expression as a distinctive transcriptional signature for studies in polyomavirus-associated nephropathy|
|Author:||Sigdel, Tara K.|
Bestard Matamoros, Oriol
Torras Ambròs, Joan
Tran, Tim Q.
Sarwal, Minnie M.
Malalties del ronyó
|Publisher:||Lippincott, Williams & Wilkins|
|Abstract:||Background: polyomavirus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. To identify PVAN-specific gene expression and underlying molecular mechanisms, we analyzed kidney biopsies with and without PVAN. Methods: the study included 168 posttransplant renal allograft biopsies (T cell-mediated rejection [TCMR] = 26, PVAN = 10, normal functioning graft = 73, and interstitial fibrosis/tubular atrophy = 59) from 168 unique kidney allograft recipients. We performed gene expression assays and bioinformatics analysis to identify a set of PVAN-specific genes. Validity and relevance of a subset of these genes are validated by quantitative polymerase chain reaction and immunohistochemistry. Results: unsupervised hierarchical clustering analysis of all the biopsies revealed high similarity between PVAN and TCMR gene expression. Increased statistical stringency identified 158 and 252 unique PVAN and TCMR injury-specific gene transcripts respectively. Although TCMR-specific genes were overwhelmingly involved in immune response costimulation and TCR signaling, PVAN-specific genes were mainly related to DNA replication process, RNA polymerase assembly, and pathogen recognition receptors. A principal component analysis (PCA) using these genes further confirmed the most optimal separation between the 3 different clinical phenotypes. Validation of 4 PVAN-specific genes (RPS15, complement factor D, lactotransferrin, and nitric oxide synthase interacting protein) by quantitative polymerase chain reaction and confirmation by immunohistochemistry of 2 PVAN-specific proteins with antiviral function (lactotransferrin and IFN-inducible transmembrane 1) was done. Conclusions: in conclusion, even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, PVAN-specific genes were identified with well-known antiviral properties that provide tools for discerning PVAN and AR as well as attractive targets for rational drug design.|
|Note:||Versió postprint del document publicat a: https://doi.org/10.1097/TP.0000000000001214|
|It is part of:||Transplantation, 2016, vol. 100, num. 10, p. 2062-2070|
|Appears in Collections:||Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))|
Articles publicats en revistes (Ciències Clíniques)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.