Prostaglandin E2 receptor EP2 mediates the effect of cyclooxygenase 2 on secondary parathyroid hyperplasia in end-stage renal disease

Zhang, Qian; Li, Shensen; Ye, Guoxin; Wang, Mengjing; Ni, Li; Kan, S; Chen, Jing

doi:10.1093/ndt/gfy194

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…Inhibitors of the PGE2 receptor 2 subtype (EP2) attenuated hyperparathyroidism induced by high phosphate. Accordingly, PGE2 or EP2 agonists directly stimulated hyperparathyroidism, suggesting that COX2 downstream PGE2 and its receptor EP2 play important roles in high phosphate-induced parathyroid cell proliferation [ 106 ].…”

Section: Post-receptor Mechanisms Of Parathyroid Cell Proliferatiomentioning

confidence: 99%

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Naveh-Many

Volovelsky

2020

IJMS

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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-α-epidermal growth factor receptor (TGF-α-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.

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Section: Post-receptor Mechanisms Of Parathyroid Cell Proliferatiomentioning

confidence: 99%

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Naveh-Many

Volovelsky

2020

IJMS

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“…Multiple lines of evidence imply that cyclooxygenase 2(COX2), its metabolite prostaglandin E2 (PGE2) as well as its receptor EP2 enhance cell growth in SHPT patients with CKD ( Zhang et al, 2011 ; Zhang et al, 2019 ). This is a potential therapeutic target for secondary hyperparathyroidism.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism

et al. 2022

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A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.

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“…Inhibitors of the PGE2 receptor 2 subtype (EP2) attenuated hyperparathyroidism induced by high phosphate. PGE2 or EP2 agonist directly stimulated hyperparathyroidism, suggesting that COX2 downstream PGE2 and its receptor EP2 play a role in the high phosphateinduced parathyroid hyperplasia of SHP [147] (Figure 3).…”

Section: Cyclooxygenase 2-pge2mentioning

confidence: 98%

Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease

et al. 2022

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Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that induces morbidity and mortality in patients. How CKD stimulates the parathyroid to increase parathyroid hormone (PTH) secretion, gene expression and cell proliferation remains an open question. In experimental SHP, the increased PTH gene expression is post-transcriptional and mediated by PTH mRNA–protein interactions that promote PTH mRNA stability. These interactions are orchestrated by the isomerase Pin1. Pin1 participates in conformational change-based regulation of target proteins, including mRNA-binding proteins. In SHP, Pin1 isomerase activity is decreased, and thus, the Pin1 target and PTH mRNA destabilizing protein KSRP fails to bind PTH mRNA, increasing PTH mRNA stability and levels. An additional level of post-transcriptional regulation is mediated by microRNA (miRNA). Mice with parathyroid-specific knockout of Dicer, which facilitates the final step in miRNA maturation, lack parathyroid miRNAs but have normal PTH and calcium levels. Surprisingly, these mice fail to increase serum PTH in response to hypocalcemia or uremia, indicating a role for miRNAs in parathyroid stimulation. SHP often leads to parathyroid hyperplasia. Reduced expressions of parathyroid regulating receptors, activation of transforming growth factor α-epidermal growth factor receptor, cyclooxygenase 2-prostaglandin E2 and mTOR signaling all contribute to the enhanced parathyroid cell proliferation. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. This review summarizes the current knowledge on the mechanisms that stimulate the parathyroid cell at multiple levels in SHP.

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Prostaglandin E2 receptor EP2 mediates the effect of cyclooxygenase 2 on secondary parathyroid hyperplasia in end-stage renal disease

Abstract: The COX2 downstream PGE2 and its receptor EP2 may play an important role in HPi-induced parathyroid hyperplasia and may serve as a potential therapeutic target for SHPT in ESRD.

Cited by 6 publications

References 42 publications

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism

Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease

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