Karyopherins: potential biological elements involved in the delayed graft function in renal transplant recipients
| العنوان: | Karyopherins: potential biological elements involved in the delayed graft function in renal transplant recipients |
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| المؤلفون: | Loreto Gesualdo, Nicola Ancona, Gianluigi Zaza, Antonio Lupo, Federica Rascio, Simona Granata, Giuseppe Grandaliano, Matteo Accetturo, Patrizia Stifanelli, Paola Pontrelli |
| المصدر: | BMC Medical Genomics BMC medical genomics 7 (2014). doi:10.1186/1755-8794-7-14 info:cnr-pdr/source/autori:Zaza, Gianluigi L.; Rascio, Federica; Pontrelli, Paola; Granata, Simona; Stifanelli, Patrizia F.; Accetturo, Matteo; Ancona, Nicola; Gesualdo, L.; Lupo, Antonio; Grandaliano, Giuseppe/titolo:Karyopherins: Potential biological elements involved in the delayed graft function in renal transplant recipients/doi:10.1186%2F1755-8794-7-14/rivista:BMC medical genomics/anno:2014/pagina_da:/pagina_a:/intervallo_pagine:/volume:7 |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Male, STAT3 Transcription Factor, Microarray, delayed graft function, renal transplantation, microarray, Delayed Graft Function, Biology, Karyopherins, Bioinformatics, Peripheral blood mononuclear cell, medicine, Genetics, Humans, Genetics(clinical), Phosphorylation, STAT3, Genetics (clinical), Kidney transplantation, Demography, Cell Nucleus, Principal Component Analysis, Interleukin-6, Gene Expression Profiling, Renal transplantation, Middle Aged, medicine.disease, Kidney Transplantation, Transplantation, Cell nucleus, Protein Transport, medicine.anatomical_structure, Immunology, biology.protein, Leukocytes, Mononuclear, Female, Nuclear transport, Transcriptome, Research Article, Signal Transduction |
| الوصف: | Background: Immediately after renal transplantation, patients experience rapid and significant improvement of their clinical conditions and undergo considerable systemic and cellular modifications. However, some patients present a slow recovery of the renal function commonly defined as delayed graft function (DGF). Although clinically well characterized, the molecular mechanisms underlying this condition are not totally defined, thus, we are currently missing specific clinical markers to predict and to make early diagnosis of this event. Methods. We investigated, using a pathway analysis approach, the transcriptomic profile of peripheral blood mononuclear cells (PBMC) from renal transplant recipients with DGF and with early graft function (EGF), before (T0) and 24 hours (T24) after transplantation. Results: Bioinformatics/statistical analysis showed that 15 pathways (8 up-regulated and 7 down-regulated) and 11 pathways (5 up-regulated and 6 down-regulated) were able to identify DGF patients at T0 and T24, respectively. Interestingly, the most up-regulated pathway at both time points was NLS-bearing substrate import into nucleus, which includes genes encoding for several subtypes of karyopherins, a group of proteins involved in nucleocytoplasmic transport. Signal transducers and activators of transcription (STAT) utilize karyopherins-alpha (KPNA) for their passage from cytoplasm into the nucleus. In vitro functional analysis demonstrated that in PBMCs of DGF patients, there was a significant KPNA-mediated nuclear translocation of the phosphorylated form of STAT3 (pSTAT3) after short-time stimulation (2 and 5 minutes) with interleukin-6. Conclusions: Our study suggests the involvement, immediately before transplantation, of karyopherin-mediated nuclear transport in the onset and development of DGF. Additionally, it reveals that karyopherins could be good candidates as potential DGF predictive clinical biomarkers and targets for pharmacological interventions in renal transplantation. However, because of the low number of patients analyzed and some methodological limitations, additional studies are needed to validate and to better address these points. © 2014 Zaza et al.; licensee BioMed Central Ltd. |
| اللغة: | English |
| تدمد: | 1755-8794 |
| DOI: | 10.1186/1755-8794-7-14 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9afdf02568ce050d371e14e8c6b30fcTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c9afdf02568ce050d371e14e8c6b30fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17558794 |
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| DOI: | 10.1186/1755-8794-7-14 |