Frontiers in Medicine | |
PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes as Potential Rejection Biomarkers After Kidney Transplantation | |
article | |
Isabel Legaz1  Carmen Botella2  Antonio Parrado2  María Rosa Moya-Quiles2  Alfredo Minguela2  Santiago Llorente3  Jesús de la Peña-Moral4  Manuel Muro2  María Victoria Bernardo2  Rafael Alfaro2  Helios Martínez-Banaclocha2  Jose Antonio Galián2  Victor Jimenez-Coll2  Francisco Boix2  Anna Mrowiec2  Diego Salmeron5  | |
[1] Department of Legal and Forensic Medicine, Faculty of Medicine, Biomedical Research Institute (IMIB), University of Murcia;Department of Immunology, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB);Department of Nephrology, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB);Department of Pathology Services, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB);Departamento de Ciencias Sociosanitarias, Universidad de Murcia;Centro de Investigación Biomédica en Red (CIBER) Epidemiología y Salud Pública (CIBERESP);Instituto Murciano de Investigacion Biomédica-Arrixaca | |
关键词: mTOR; Gene expression; medico-legal autopsy; antibody-mediated rejection; PCR array; | |
DOI : 10.3389/fmed.2021.547849 | |
学科分类:社会科学、人文和艺术(综合) | |
来源: Frontiers | |
【 摘 要 】
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.
【 授权许可】
CC BY
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