Integrated transcriptomic and proteomic analyses for the characterization of parathyroid oxyphil cells in uremic patients.
Calcimimetics
Calcitriol
Mitochondrion
Parathyroid oxyphil cell
Proteomic
Transcriptomic
Journal
Amino acids
ISSN: 1438-2199
Titre abrégé: Amino Acids
Pays: Austria
ID NLM: 9200312
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
received:
02
07
2021
accepted:
10
01
2022
pubmed:
30
3
2022
medline:
9
6
2022
entrez:
29
3
2022
Statut:
ppublish
Résumé
Chief cells are the predominant cells in parathyroid glands of healthy adults; however, parathyroid oxyphil cells, whose function is unknown, increase dramatically in patients with secondary hyperparathyroidism (SHPT). Calcitriol and calcimimetics are the most powerful treatments for SHPT, while the mechanisms leading to calcitriol or calcimimetic resistance in oxyphil cell-predominant SHPT are unknown. Here we used transcriptomic and proteomic techniques to characterize oxyphil cells by comparing the differences between chief and oxyphil cell nodules of parathyroid glands in uremic patients. Compared to chief cell nodules, the most marked expression increases in oxyphil cell nodules were for mitochondrion-associated proteins. The mitochondria number and mitochondrial DNA content were also significantly increased in oxyphil cell nodules. Moreover, oxyphil cell nodules expressed parathyroid-specific factors, and exhibited lower levels of proliferation-related proteins but higher synthesis and secretion level of parathyroid hormone (PTH). The protein expression of SHPT-regulating factors, including vitamin-D receptor, calcium-sensing receptor and Klotho, were significantly downregulated in oxyphil cell nodules. Therefore, oxyphil cells characterized by enrich mitochondria in uremic patients showed higher synthesis and secretion of PTH but lower expression of SHPT regulators than chief cells, which may contribute to the pathophysiology of SHPT and the treatment resistance to calcitriol and calcimimetics.
Identifiants
pubmed: 35348903
doi: 10.1007/s00726-022-03126-8
pii: 10.1007/s00726-022-03126-8
doi:
Substances chimiques
Parathyroid Hormone
0
Calcitriol
FXC9231JVH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
749-763Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
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