Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis.
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.
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Irena
I
Týcová
Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Hemodialysis Centre, University Hospital, Hradec Králové, Czech Republic.
Sylvie Dusilová
SD
Sulková
Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Jitka
J
Štěpánková
Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
Zdeněk
Z
Krejčík
Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
Michaela Dostálová
MD
Merkerová
Institute of Inherited Metabolic Disorders, Charles University and 1st School of Medicine and General University Hospital, Prague, Czech Republic.
Viktor
V
Stránecký
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Petra
P
Hrubá
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Eva
E
Girmanová
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Marek
M
Černoch
Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Květoslav
K
Lipár
Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Tomáš
T
Marada
Department of Pathology, Charles University and 1st School of Medicine and General University Hospital, Prague, Czech Republic; and.
Ctibor
C
Povýšil
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; ondrej.viklicky@ikem.cz.
Ondřej
O
Viklický
D000328:Adult; D000368:Aged; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000473:pathology; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D010280:Parathyroid Glands / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D006435:Renal Dialysis; D059467:Transcriptome / Q000235:genetics
D010281:Parathyroid Hormone; D012333:RNA, Messenger
diffuse parathyroid hyperplasia; microarray; nodular parathyroid hyperplasia