NF-κB activation contributes to parathyroid cell proliferation in chronic kidney disease

Kan, S; Zhang, Weichen; Mao, Jianping; Wang, Mengjing; Ni, Li; Zhang, Qian; Chen, Jing

doi:10.1007/s40620-018-0530-2

Cited by 17 publications

(9 citation statements)

References 53 publications

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“…NF-κB contributes to the pathogenesis of primary parathyroid hyperplasia [ 99 ]. In CKD-induced SHP, parathyroid glands from patients on dialysis showed activation of the NF-κB pathway in the nodular hyperplastic glands, with a significantly higher increase in diffuse hyperplastic glands [ 100 ]. In 5/6 nephrectomized rats fed a high-phosphorus diet, Proliferating cell nuclear antigen (PCNA) levels and activation of the NF-κB pathway were higher compared with the sham group, and VDR levels were decreased as expected.…”

Section: Post-receptor Mechanisms Of Parathyroid Cell Proliferatiomentioning

confidence: 99%

“…1,25D decreased serum PTH and parathyroid cell proliferation together with reduced activation of the NF-κB pathway. A selective NF-κB inhibitor PDTC (ammonium pyrrolidinedithiocarbamate) decreased parathyroid NF-κB pathway activation, serum PTH, parathyroid cell proliferation, and the enlargement of the parathyroid glands in 5/6 nephrectomized rats [ 100 ]. These findings suggest that NF-κB contributes to parathyroid cell proliferation.…”

Section: Post-receptor Mechanisms Of Parathyroid Cell Proliferatiomentioning

confidence: 99%

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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%

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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“…NF-κB contributes to the pathogenesis of primary parathyroid hyperplasia [140]. In CKD-induced SHP, there was activation of the NF-κB pathway in the nodular hyperplastic parathyroid glands from patients on dialysis, with a significant increase in diffuse hyperplasia glands [141]. The reduction in VDR could lead to activation of the NF-κB pathway.…”

Section: Nuclear Factor-kappa Bmentioning

confidence: 99%

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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“…In regard to the signaling mechanisms involved in the development of parathyroid hyperplasia, a recent study by Kan et al . reported that vitamin D deficiency promotes activation of nuclear factor kappa B (NFκB) both in parathyroid glands from patients on hemodialysis and in experimental models of uremia 23 . Given that vitamin D also inhibits NFκB in other tissues 24 , this might represent an additional benefit of vitamin D supplementation in the management of SHPT.…”

Section: Novel Insights Into the Pathogenesis Of Secondary Hyperparatmentioning

confidence: 99%

Recent advances in understanding and managing secondary hyperparathyroidism in chronic kidney disease

Rodríguez‐Ortiz

Rodríguez

2020

F1000Res

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Secondary hyperparathyroidism is a complex pathology that develops as chronic kidney disease progresses. The retention of phosphorus and the reductions in calcium and vitamin D levels stimulate the synthesis and secretion of parathyroid hormone as well as the proliferation rate of parathyroid cells. Parathyroid growth is initially diffuse but it becomes nodular as the disease progresses, making the gland less susceptible to be inhibited. Although the mechanisms underlying the pathophysiology of secondary hyperparathyroidism are well known, new evidence has shed light on unknown aspects of the deregulation of parathyroid function. Secondary hyperparathyroidism is an important feature of chronic kidney disease–mineral and bone disorder and plays an important role in the development of bone disease and vascular calcification. Thus, part of the management of chronic kidney disease relies on maintaining acceptable levels of mineral metabolism parameters in an attempt to slow down or prevent the development of secondary hyperparathyroidism. Here, we will also review the latest evidence regarding several aspects of the clinical and surgical management of secondary hyperparathyroidism.

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NF-κB activation contributes to parathyroid cell proliferation in chronic kidney disease

Abstract: NF-κB plays an important role in PG hyperplasia progression. VDR deficiency may be involved in the parathyroid gland hyperplasia through the activation of NF-κB pathway.

Cited by 17 publications

References 53 publications

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease

Recent advances in understanding and managing secondary hyperparathyroidism in chronic kidney disease

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