Publication:
PCR Array technology in biopsy samples identifies up-regulated mTOR pathway genes as potential rejection biomarkers after kidney transplantation

Simple item page
dc.contributor.authorBernardo, María Victoria
dc.contributor.authorAlfaro, Rafael
dc.contributor.authorMartínez Banaclocha, Helios
dc.contributor.authorGalián, Jose Antonio
dc.contributor.authorJiménez Coll, Víctor
dc.contributor.authorBoix, Francisco
dc.contributor.authorMrowiec, Anna
dc.contributor.authorSalmeron, Diego
dc.contributor.authorBotella, Carmen
dc.contributor.authorParrado, Antonio
dc.contributor.authorMoya Quiles, María Rosa
dc.contributor.authorMinguela, Alfredo
dc.contributor.authorLlorente, Santiago
dc.contributor.authorPeña Moral, Jesús de la
dc.contributor.authorMuro, Manuel
dc.contributor.authorLegaz Pérez, Isabel
dc.contributor.departmentCiencias Sociosanitarias
dc.date.accessioned2024-07-11T10:46:08Z
dc.date.available2024-07-11T10:46:08Z
dc.date.issued2021-02-17
dc.description© 2021 Legaz, Bernardo, Alfaro, Martínez-Banaclocha, Galián, Jimenez-Coll, Boix, Mrowiec, Salmeron, Botella, Parrado, Moya-Quiles, Minguela, Llorente, Peña-Moral and Muro. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Frontiers in Medicine. To access the final edited and published work see https://doi.org/10.3389/fmed.2021.547849
dc.description.abstractBackground: Antibody-mediated rejection (AMR) is the major cause of kidney transplant rejection. The donor-specific human leukocyte antigen (HLA) antibody (DSA) response to a renal allograft is not fully understood yet. mTOR complex has been described in the accommodation or rejection of transplants and integrates responses from a wide variety of signals. The aim of this study was to analyze the expression of the mTOR pathway genes in a large cohort of kidney transplant patients to determine its possible influence on the transplant outcome. Methods: A total of 269 kidney transplant patients monitored for DSA were studied. The patients were divided into two groups, one with recipients that had transplant rejection (+DSA/+AMR) and a second group of recipients without rejection (+DSA/–AMR and –DSA/–AMR, controls). Total RNA was extracted from kidney biopsies and reverse transcribed to cDNA. Human mTOR-PCR array technology was used to determine the expression of 84 mTOR pathway genes. STRING and REVIGO software were used to simulate gene to gene interaction and to assign a molecular function. Results: The studied groups showed a different expression of the mTOR pathway related genes. Recipients that had transplant rejection showed an over-expressed transcript (≥5-fold) of AKT1S1, DDIT4, EIF4E, HRAS, IGF1, INS, IRS1, PIK3CD, PIK3CG, PRKAG3, PRKCB (>12-fold), PRKCG, RPS6KA2, TELO2, ULK1, and VEGFC, compared with patients that did not have rejection. AKT1S1 transcripts were more expressed in +DSA/–AMR biopsies compared with +DSA/+AMR. The main molecular functions of up-regulated gene products were phosphotransferase activity, insulin-like grown factor receptor and ribonucleoside phosphate binding. The group of patients with transplant rejection also showed an under-expressed transcript (≥5-fold) of VEGFA (>15-fold), RPS6, and RHOA compared with the group without rejection. The molecular function of down-regulated gene products such as protein kinase activity and carbohydrate derivative binding proteins was also analyzed. Conclusions: We have found a higher number of over-expressed mTOR pathway genes than under-expressed ones in biopsies from rejected kidney transplants (+DSA/+AMR) with respect to controls. In addition to this, the molecular function of both types of transcripts (over/under expressed) is different. Therefore, further studies are needed to determine if variations in gene expression profiles can act as predictors of graft loss, and a better understanding of the mechanisms of action of the involved proteins would be necessary.es
dc.formatapplication/pdfes
dc.format.extent18es
dc.identifier.citationFront. Med. 8:547849
dc.identifier.doihttps://doi.org/ 10.3389/fmed.2021.547849
dc.identifier.issnElectronic: 2296-858X
dc.identifier.urihttp://hdl.handle.net/10201/143005
dc.languageenges
dc.publisherFrontiers Media
dc.relationOur work was possible thanks to the support from Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness. Grant Nos. PI15/01370 and P19/01194 and co-funding of the European Union with European Fund of Regional Development (FEDER) with the principle of A manner to build Europe.es
dc.relation.publisherversionhttps://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.547849/full
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectmTORes
dc.subjectGene expressiones
dc.subjectMedico-legal autopsyes
dc.subjectAntibody-mediated rejectiones
dc.subjectPCR arrayes
dc.titlePCR Array technology in biopsy samples identifies up-regulated mTOR pathway genes as potential rejection biomarkers after kidney transplantationes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublicationb83b4b59-2d61-40f0-9108-5c6a6d158295
relation.isAuthorOfPublication.latestForDiscoveryb83b4b59-2d61-40f0-9108-5c6a6d158295
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
fmed-08-547849.pdf
Size:
2.36 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.26 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Artículos