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Title: Intragraft antiviral-specific gene expression as a distinctive transcriptional signature for studies in polyomavirus-associated nephropathy
Author: Sigdel, Tara K.
Bestard Matamoros, Oriol
Salomonis, Nathan
Hsieh, Szu-Chuan
Torras Ambròs, Joan
Naesens, Maarten
Tran, Tim Q.
Roedder, Silke
Sarwal, Minnie M.
Keywords: Antígens
Malalties del ronyó
Trasplantament renal
Efectes secundaris
Kidney diseases
Kidney transplantation
Side effects
Issue Date: Oct-2016
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:
It is part of: Transplantation, 2016, vol. 100, num. 10, p. 2062-2070
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ISSN: 0041-1337
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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