Publication: PCR Array technology in biopsy samples identifies up-regulated mTOR pathway genes as potential rejection biomarkers after kidney transplantation
Authors
Bernardo, María Victoria ; Alfaro, Rafael ; Martínez Banaclocha, Helios ; Galián, Jose Antonio ; Jiménez Coll, Víctor ; Boix, Francisco ; Mrowiec, Anna ; Salmeron, Diego ; Botella, Carmen ; Parrado, Antonio ; Moya Quiles, María Rosa ; Minguela, Alfredo ; Llorente, Santiago ; Peña Moral, Jesús de la ; Muro, Manuel ; Legaz Pérez, Isabel
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Publisher
Frontiers Media
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DOI
https://doi.org/ 10.3389/fmed.2021.547849
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info:eu-repo/semantics/article
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
Abstract
Background: 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.
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Front. Med. 8:547849
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/