Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27600827
DOI
10.1152/ajpendo.00517.2015
PII: ajpendo.00517.2015
Knihovny.cz E-resources
- Keywords
- diffuse parathyroid hyperplasia, microarray, nodular parathyroid hyperplasia,
- MeSH
- Kidney Failure, Chronic complications therapy MeSH
- Renal Dialysis * MeSH
- Adult MeSH
- Focal Nodular Hyperplasia etiology genetics therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger biosynthesis genetics MeSH
- Multigene Family genetics MeSH
- Parathyroid Hormone blood MeSH
- Parathyroid Glands pathology MeSH
- Parathyroidectomy MeSH
- Hyperparathyroidism, Primary pathology MeSH
- Gene Expression Regulation genetics MeSH
- Hyperparathyroidism, Secondary etiology genetics therapy MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Transcriptome genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- RNA, Messenger MeSH
- Parathyroid Hormone 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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