Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27600827
DOI
10.1152/ajpendo.00517.2015
PII: ajpendo.00517.2015
Knihovny.cz E-zdroje
- Klíčová slova
- diffuse parathyroid hyperplasia, microarray, nodular parathyroid hyperplasia,
- MeSH
- chronické selhání ledvin komplikace terapie MeSH
- dialýza ledvin * MeSH
- dospělí MeSH
- fokální nodulární hyperplazie etiologie genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA biosyntéza genetika MeSH
- multigenová rodina genetika MeSH
- parathormon krev MeSH
- paratyreoidea patologie MeSH
- paratyreoidektomie MeSH
- primární hyperparatyreóza patologie MeSH
- regulace genové exprese genetika MeSH
- sekundární hyperparatyreóza etiologie genetika terapie MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transkriptom genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- messenger RNA MeSH
- parathormon MeSH
Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients compared with the transplant cohort and primary hyperparathyroidism; therefore, further experiments were performed in hemodialysis patients only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyroid hyperplasia revealed highly significant differences in Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes database in ribosome structure (P = 3.70 × 10-18). Next, quantitative RT-PCR validation of the top differently expressed genes from microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF; P < 0.001), calcyclin-binding protein (CACYBP; P < 0.05), and exocyst complex component 8 (EXOC8; P < 0.05) and lower expression of peptidylprolyl cis/trans-isomerase and NIMA-interacting 1 (PIN1; P < 0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed higher RANGRF and lower PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. In conclusion, our study suggests the RANGRF transcript, which controls RNA metabolism, to be likely involved in pathways associated with the switch to nodular parathyroid growth. This transcript, along with PIN1 transcript, which influences parathyroid hormone secretion, may represent new therapeutical targets to cure secondary hyperparathyroidism.
Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic
Transplant Surgery Department Institute for Clinical and Experimental Medicine Prague Czech Republic
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