PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes as Potential Rejection Biomarkers After Kidney Transplantation
| العنوان: | PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes as Potential Rejection Biomarkers After Kidney Transplantation |
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| المؤلفون: | Isabel Legaz, María Victoria Bernardo, Rafael Alfaro, Helios Martínez-Banaclocha, Jose Antonio Galián, Victor Jimenez-Coll, Francisco Boix, Anna Mrowiec, Diego Salmeron, Carmen Botella, Antonio Parrado, María Rosa Moya-Quiles, Alfredo Minguela, Santiago Llorente, Jesús de la Peña-Moral, Manuel Muro |
| المصدر: | Frontiers in Medicine, Vol 8 (2021) Frontiers in Medicine |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, medico-legal autopsy, Human leukocyte antigen, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Gene interaction, Gene expression, medicine, PI3K/AKT/mTOR pathway, Kidney transplantation, Original Research, lcsh:R5-920, DDIT4, biology, business.industry, PCR array, General Medicine, Carbohydrate derivative binding, medicine.disease, Transplant rejection, 030104 developmental biology, biology.protein, Cancer research, mTOR, antibody-mediated rejection, Medicine, business, lcsh:Medicine (General) |
| الوصف: | 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. |
| تدمد: | 2296-858X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::980f4969bc1ce040ff2f6a6cd0f274a0 https://pubmed.ncbi.nlm.nih.gov/33681239 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....980f4969bc1ce040ff2f6a6cd0f274a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2296858X |
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