PMID- 33681239
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240331
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 8
DP  - 2021
TI  - PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes 
      as Potential Rejection Biomarkers After Kidney Transplantation.
PG  - 547849
LID - 10.3389/fmed.2021.547849 [doi]
LID - 547849
AB  - 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.
CI  - Copyright (c) 2021 Legaz, Bernardo, Alfaro, Martinez-Banaclocha, Galian, 
      Jimenez-Coll, Boix, Mrowiec, Salmeron, Botella, Parrado, Moya-Quiles, Minguela, 
      Llorente, Pena-Moral and Muro.
FAU - Legaz, Isabel
AU  - Legaz I
AD  - Department of Legal and Forensic Medicine, Faculty of Medicine, Biomedical 
      Research Institute (IMIB), University of Murcia, Murcia, Spain.
FAU - Bernardo, Maria Victoria
AU  - Bernardo MV
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Alfaro, Rafael
AU  - Alfaro R
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Martinez-Banaclocha, Helios
AU  - Martinez-Banaclocha H
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Galian, Jose Antonio
AU  - Galian JA
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Jimenez-Coll, Victor
AU  - Jimenez-Coll V
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Boix, Francisco
AU  - Boix F
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Mrowiec, Anna
AU  - Mrowiec A
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Salmeron, Diego
AU  - Salmeron D
AD  - Departamento de Ciencias Sociosanitarias, Universidad de Murcia, Murcia, Spain.
AD  - Centro de Investigacion Biomedica en Red (CIBER) Epidemiologia y Salud Publica 
      (CIBERESP), Murcia, Spain.
AD  - Instituto Murciano de Investigacion Biomedica-Arrixaca, Murcia, Spain.
FAU - Botella, Carmen
AU  - Botella C
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Parrado, Antonio
AU  - Parrado A
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Moya-Quiles, Maria Rosa
AU  - Moya-Quiles MR
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Minguela, Alfredo
AU  - Minguela A
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Llorente, Santiago
AU  - Llorente S
AD  - Department of Nephrology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - de la Pena-Moral, Jesus
AU  - de la Pena-Moral J
AD  - Department of Pathology Services, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
FAU - Muro, Manuel
AU  - Muro M
AD  - Department of Immunology, University Clinical Hospital Virgen de la 
      Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
LA  - eng
SI  - figshare/10.6084/m9.figshare.14020901
PT  - Journal Article
DEP - 20210217
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC7927668
OTO - NOTNLM
OT  - Gene expression
OT  - PCR array
OT  - antibody-mediated rejection
OT  - mTOR
OT  - medico-legal autopsy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/09 06:00
MHDA- 2021/03/09 06:01
PMCR- 2021/02/17
CRDT- 2021/03/08 05:55
PHST- 2020/03/31 00:00 [received]
PHST- 2021/01/27 00:00 [accepted]
PHST- 2021/03/08 05:55 [entrez]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2021/03/09 06:01 [medline]
PHST- 2021/02/17 00:00 [pmc-release]
AID - 10.3389/fmed.2021.547849 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2021 Feb 17;8:547849. doi: 10.3389/fmed.2021.547849. 
      eCollection 2021.