title: Progression of secondary hyperparathyroidism involves deregulation of genes related to DNA and RNA stability.
abstract: BACKGROUND
  Renal secondary hyperparathyroidism in its late stages becomes autonomous, so excessive parathyroid hormone (PTH) secretion no longer responds to physiologic stimuli or to aggressive medical treatment.
  
  
  METHODS
  To gain molecular understanding of progression of renal secondary hyperparathyroidism, normal and hyperplastic parathyroid tissue with diffuse and nodular growth were analyzed. The results were also compared to parathyroid adenomas. The analysis was performed by high-density oligonucleotide microarray and bidirectional subtraction library.
  
  
  RESULTS
  Analysis of the DNA arrays found 16 overexpressed and 132 repressed genes in the nodules while the subtraction library produced 34 overexpressed and 40 repressed genes. The differentially expressed genes between diffuse and nodular samples included some related to DNA stability and repair (TALDO1, PRDX2, DDB1, XRCC1, and POLB), RNA stability and degradation (OASL and AUF1), protein synthesis and processing (PFDN5, HSPD1, and NACA), cell growth (CDC25C and GRPR), and tumorigenesis and cell cycle (VIL2 and TPD52).
  
  
  CONCLUSIONS
  According to the function described for the deregulated genes, when secondary hyperparathyroidism becomes autonomous and refractory to treatment, RNA degradation may be increased while DNA integrity may be compromised. These two mechanisms, combined with deregulation of genes related to growth and differentiation show the complex pathway of parathyroid glands' evolution in renal hyperparathyroidism and may explain the large amount of molecular cytogenetic aberrations found in refractory hyperparathyroidism. Considering that some of the genes with altered expression in nodular hyperplasia lead to irreversible consequences in the genomic integrity of the cells, an adequate and early management of the secondary hyperparathyroidism of chronic kidney disease becomes mandatory.
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain. isr@hca.es
authors.forename: Iñigo
authors.initials: I
authors.lastname: Santamaría
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvarez-Hernández
authors.forename: Rosa
authors.initials: R
authors.lastname: Jofré
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Polo
authors.forename: Javier
authors.initials: J
authors.lastname: Menárguez
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Cannata-Andía
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D049109:Cell Proliferation; D002648:Child; D016000:Cluster Analysis; D004247:DNA / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D042822:Genomic Instability; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000235:genetics*; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000473:pathology; D020871:RNA Stability; D018167:Receptors, Calcitriol / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics
chemical_list: C095550:CASR protein, human; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D004247:DNA