Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia

Shi, Yuhong; Hogue, Joyce A.; Dixit, Darshana; Koh, James; Olson, John A.

doi:10.1073/pnas.1319742111

Cited by 52 publications

(48 citation statements)

References 26 publications

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“…With the rise of circulating calcium levels, a classic endocrine feedback loop occurs, whereby the CaSRs and its signalling pathway are reactivated, silencing PTH secretion 7 33 80 141 168 169. In HPT, various alterations inactivating CaSR signalling pathway can occur, causing excess PTH secretion 7 11 13 33 42 78 81 141 166. Furthermore, if downregulation of CaSR persists over time, studies have shown that it can lead to aberrant cell growth and proliferation (thought to be related to aberrant Wnt/β-catenin and cyclin D1 signalling), suggesting that CaSR signalling may serve a tumour suppressor function in the parathyroid glands 7 11 33 42 78 81 141 152 166 170–172…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

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Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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“…Western blot was performed as previously described [19] . Anti-extracellular regulated kinase (ERK) 1/2, anti-phospho-ERK1/2, anti-β-actin and horseradish peroxidase-conjugated anti-IgG were purchased from Cell Signaling Technology (Danvers, Mass., USA).…”

Section: Western Blotmentioning

confidence: 99%

Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation

Qin¹,

Bajinka²,

Xiao-ai³

et al. 2015

Int Arch Allergy Immunol

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Background: Infection of human bronchial epithelial cells (hBECs) with respiratory syncytial virus (RSV) has been shown to induce a Th lymphocyte subset drift, e.g. enhanced differentiation of Th2 and Th17 subsets, which is a classic characteristic of asthma. However, the molecules responsible for the drift in Th subsets remain unknown. This study aims to determine the expression of leptin in RSV-infected hBECs, and its role in Th2 and Th17 cell differentiation and extracellular regulated kinase (ERK) 1/2 phosphorylation. Methods: Cultured hBECs were infected with RSV. mRNA expression of the LEP gene in cells was measured by real-time PCR while LEP protein secretion in culture medium was measured by ELISA. Th differentiation was investigated in cultured human peripheral blood mononuclear cells following stimulation with recombinant human leptin. Th2 and Th17 subsets were examined by flow cytometry. Phosphorylation of the ERK1/2 protein in lymphocytes was detected by Western blot and immunofluorescence. Results: LEP mRNA expression was significantly upregulated in RSV-infected hBECs while the leptin protein level in the supernatants of RSV-infected hBECs was significantly increased. Stimulation of lymphocytes with leptin increased the differentiation of the Th17 subset and ERK1/2 phosphorylation, but suppressed Th2 subset differentiation. Conclusion: Leptin was oversecreted by RSV-infected hBECs, which promoted Th17 subset differentiation but suppressed Th2 subset differentiation possibly via regulating ERK1/2 phosphorylation.

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“…Forty-eight hours later, cells were harvested, homogenized, and subjected to Western blot analysis of Piezo1 protein expression following the previous protocol [16]. Briefly, the treated HUVECs were homogenized in lysis buffer (1% SDS, 10 mM Tris pH 8.0, 130 mM NaCl, 5 mM EDTA) containing protease inhibitors.…”

Section: Western Blot Of Piezo1 Protein Expressionmentioning

confidence: 99%

MiR-103a targeting Piezo1 is involved in acute myocardial infarction through regulating endothelium function

Huang

Chen

et al. 2013

Cardiol J.

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Background: Acute myocardial infarction (AMI) is commonly known as the heart attack. The molecular events involved in the development of AMI remain unclear. This study was to investigate the expression of miR-103a in patients with high blood pressure (HBP) and AMI patients with and without HBP, as well as its effect on endothelial cell functions. Methods: MiR-103a expression in plasma and peripheral blood mononuclear cells (PBMCs) was measured by real-time polymerase chain reaction (PCR). The regulatory effect of miR-103a on Piezo1 gene was identified by a luciferase reporter system. The role of miR-103a in en- (Cardiol J 2016; 23, 5: 556-562)

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Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia

Cited by 52 publications

References 26 publications

Clinicopathological correlates of hyperparathyroidism

Clinicopathological correlates of hyperparathyroidism

Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation

MiR-103a targeting Piezo1 is involved in acute myocardial infarction through regulating endothelium function

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