PMID- 32570711
OWN - NLM
STAT- MEDLINE
DCOM- 20210215
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 12
DP  - 2020 Jun 18
TI  - Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney 
      Disease.
LID - 10.3390/ijms21124332 [doi]
LID - 4332
AB  - Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney 
      disease (CKD) that correlates with morbidity and mortality in uremic patients. It 
      is characterized by high serum parathyroid hormone (PTH) levels and impaired bone 
      and mineral metabolism. The main mechanisms underlying SHP are increased PTH 
      biosynthesis and secretion as well as increased glandular mass. The mechanisms 
      leading to parathyroid cell proliferation in SHP are not fully understood. 
      Reduced expressions of the receptors for calcium and vitamin D contribute to the 
      disinhibition of parathyroid cell proliferation. Activation of transforming 
      growth factor-alpha-epidermal growth factor receptor (TGF-alpha-EGFR), nuclear factor 
      kappa B (NF-kB), and cyclooxygenase 2- prostaglandin E2 (Cox2-PGE2) signaling all 
      correlate with parathyroid cell proliferation, underlining their roles in the 
      development of SHP. In addition, the mammalian target of rapamycin (mTOR) pathway 
      is activated in parathyroid glands of experimental SHP rats. Inhibition of mTOR 
      by rapamycin prevents and corrects the increased parathyroid cell proliferation 
      of SHP. Mice with parathyroid-specific deletion of all miRNAs have a muted 
      increase in serum PTH and fail to increase parathyroid cell proliferation when 
      challenged by CKD, suggesting that miRNA is also necessary for the development of 
      SHP. This review summarizes the current knowledge on the mechanisms of 
      parathyroid cell proliferation in SHP.
FAU - Naveh-Many, Tally
AU  - Naveh-Many T
AUID- ORCID: 0000-0002-0903-8182
AD  - Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah 
      Hebrew University Medical Center, Jerusalem 91120, Israel.
AD  - The Wohl Institute for Translational Medicine, Hadassah Hebrew University Medical 
      Center, Jerusalem 91120, Israel.
FAU - Volovelsky, Oded
AU  - Volovelsky O
AUID- ORCID: 0000-0002-5378-1045
AD  - The Wohl Institute for Translational Medicine, Hadassah Hebrew University Medical 
      Center, Jerusalem 91120, Israel.
AD  - Pediatric Nephrology Unit and Research Lab, Hadassah Hebrew University Medical 
      Center, Jerusalem 91120, Israel.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200618
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (FGF23 protein, human)
RN  - 0 (Fgf23 protein, mouse)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
SB  - IM
MH  - Cell Proliferation
MH  - Down-Regulation
MH  - Fibroblast Growth Factor-23
MH  - Humans
MH  - Hyperparathyroidism, Secondary/etiology/*metabolism/pathology
MH  - Parathyroid Glands/metabolism/*pathology
MH  - Receptors, Calcitriol/metabolism
MH  - Receptors, Calcium-Sensing/metabolism
MH  - Renal Insufficiency, Chronic/*complications/metabolism
PMC - PMC7352987
OTO - NOTNLM
OT  - calcium-sensing receptor (CaSR)
OT  - fibroblast growth factor (FGF23)
OT  - mammalian target of rapamycin (mTOR)
OT  - parathyroid hormone (PTH)
OT  - uremia
OT  - vitamin D receptor (VDR)
COIS- The authors declare no conflict of interests.
EDAT- 2020/06/24 06:00
MHDA- 2021/02/16 06:00
PMCR- 2020/06/01
CRDT- 2020/06/24 06:00
PHST- 2020/05/17 00:00 [received]
PHST- 2020/06/14 00:00 [revised]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/06/24 06:00 [entrez]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2021/02/16 06:00 [medline]
PHST- 2020/06/01 00:00 [pmc-release]
AID - ijms21124332 [pii]
AID - ijms-21-04332 [pii]
AID - 10.3390/ijms21124332 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jun 18;21(12):4332. doi: 10.3390/ijms21124332.