Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA106443 | ENA |
REPOSITORIES: ENA
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Project description:The pathogenesis of primary hyperparathyroidism (I-HPT) and secondary hyperparathyroidism (II-PTH) remains to be elucidated. To characterize their pathophysiology, we investigated the effects of calcium and phosphate on cell proliferation and PTH release in an organ culture of parathyroid tissues. Dissected parathyroid tissues obtained from patients with I-HPT (adenoma) or II-PTH (nodular hyperplasia) were precultured on a collagen-coated membrane for 1-4 week. After exchanging the medium for one containing various concentrations of phosphate, PTH release and [3H]thymidine incorporation were studied. In contrast to dispersed parathyroid cells cultured in a monolayer, calcium decreased PTH release in a concentration-dependent manner in parathyroid tissues. Furthermore, when parathyroid tissues obtained from II-PTH were precultured for 1-4 weeks, PTH release and parathyroid cell proliferation were significantly increased in high-phosphate medium. These phosphate effects were also observed to a lesser extent in parathyroid tissues obtained from I-HPT, but there was no significant difference between I-HPT and II-HPT. Microarray analyses revealed that mRNA levels of PTH, CaSR, and VDR were well preserved, and several growth factors (e.g. TGF-beta1-induced protein) were abundantly expressed in II-PTH. Using organ cultures of hyperparathyroid tissues, in which PTH release and CaSR are well preserved for a prolonged period, we have demonstrated that phosphate stimulates parathyroid cell proliferation not only in II-PTH but also in I-HPT. Although the mechanism responsible for phosphate-induced cell proliferation remains to be elucidated, our in vitro findings suggest that both parathyroid tissues preserve to some extent a physiological response system to hyperphosphatemia as observed in normal parathyroid cells. These data will be published in Journal of Bone & Mineral Metabolism. Experiment Overall Design: Two conditioned experimets, low vs. high phosphate medium, cultured for 1 and 4 days
2008-06-20 | E-GEOD-11423 | biostudies-arrayexpress
Project description:The pathogenesis of primary hyperparathyroidism (I-HPT) and secondary hyperparathyroidism (II-PTH) remains to be elucidated. To characterize their pathophysiology, we investigated the effects of calcium and phosphate on cell proliferation and PTH release in an organ culture of parathyroid tissues. Dissected parathyroid tissues obtained from patients with I-HPT (adenoma) or II-PTH (nodular hyperplasia) were precultured on a collagen-coated membrane for 1-4 week. After exchanging the medium for one containing various concentrations of phosphate, PTH release and [3H]thymidine incorporation were studied. In contrast to dispersed parathyroid cells cultured in a monolayer, calcium decreased PTH release in a concentration-dependent manner in parathyroid tissues. Furthermore, when parathyroid tissues obtained from II-PTH were precultured for 1-4 weeks, PTH release and parathyroid cell proliferation were significantly increased in high-phosphate medium. These phosphate effects were also observed to a lesser extent in parathyroid tissues obtained from I-HPT, but there was no significant difference between I-HPT and II-HPT. Microarray analyses revealed that mRNA levels of PTH, CaSR, and VDR were well preserved, and several growth factors (e.g. TGF-beta1-induced protein) were abundantly expressed in II-PTH. Using organ cultures of hyperparathyroid tissues, in which PTH release and CaSR are well preserved for a prolonged period, we have demonstrated that phosphate stimulates parathyroid cell proliferation not only in II-PTH but also in I-HPT. Although the mechanism responsible for phosphate-induced cell proliferation remains to be elucidated, our in vitro findings suggest that both parathyroid tissues preserve to some extent a physiological response system to hyperphosphatemia as observed in normal parathyroid cells. These data will be published in Journal of Bone & Mineral Metabolism. Keywords: Organ culture experiments, dultured in low vs.high phosphate medium
2008-05-13 | GSE11423 | GEO
Project description:Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) and correlates with morbidity and mortality. In this study we profiled microRNAs (miRNA) in parathyroids from different experimental SHP models and uremic patients and studied the function of specific miRNA using antagonizing oligonucleotides (anti-miRs). miRNA profiles established by small RNA deep sequencing showed that human, rat and mouse parathyroids share the same most abundant miRNAs. Principal component analyses clearly segregated parathyroids from SHP rats from normal rats, based on their miRNA expression profiles. Similar findings were observed in hyperplastic parathyroids from CKD patients compared to normal parathyroids from patients without kidney disease. We identifed specific parathyroid miRNAs that were dysregulated in all experimental SHP models studied. let-7i was decreased and miR-141 and miR-148a were increased in the parathyroids of rats with prolonged CKD induced by an 8 w adenine high phosphorus diet. Down-regulation of let-7 by anti-miRs increased PTH secretion in normal and in CKD rats, as well as in parathyroid organ cultures. Anti-miR-148 prevented the increase in serum PTH in CKD rats and decreased secreted PTH in parathyroid organ cultures. Our findings characterized parathyroid miRNA profiles and demonstrated conservation of the abundant miRNAs in different species. The evolutionary conservation of abundant miRNAs and their regulation in SHP suggest that miRNAs are important for parathyroid function and the development of SHP. Down-regulation of let-7 and miR-148 affects PTH secretion in vivo and in vitro, suggesting a role for these miRNAs in SHP. We propose that let-7 restrains while miR-148 promotes PTH secretion. In CKD, the decrease in parathyroid let-7 and the increase in miR-148 miRNAs may contribute to the development of SHP.
2017-03-21 | GSE79727 | GEO
Project description:Whole mouse genome microarrays from Agilent were used to determine expression profile of whole organ cervical thymus, thoracic thymus and parathyroid from Foxn1-GFP; Pth-Cre; R26dTomato transgenic mice.
2015-07-31 | E-MTAB-3751 | biostudies-arrayexpress
Project description:Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting.
2015-12-01 | GSE74082 | GEO
Project description:Pulmonary hypertension (PH) is an incurable right heart failure disease. Parathyroid hormone (PTH) is secreted from the parathyroid gland and plays a crucial role in calcium homeostasis. PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We assessed whether the regulation of PTH affected PH in a hypoxia (Hx)-induced PH mouse model. PTH treatment exacerbated right ventricular hypertrophy and right ventricular systolic pressure in Hx mice. Our data showed how is PTH effected for PH model murine lung.
2023-10-11 | GSE244861 | GEO
Project description:Transcriptional profiling of human MSCs comparing control MSCs with parathyroid hormone (PTH)-stimulated MSCs. PTH-stimulated MSCs were treated with 0.1 nM recombinant human PTH (N-terminal fragment, amino acids 1-34) for 48 hours. Human MSCs were isolated from a bone marrow sample obtained from a healthy adult volunteer. Two-condition experiment: control MSCs vs. PTH-stimulated MSCs. 1 control MSCs and 1 PTH-stimulated MSCs.
2014-02-01 | E-GEOD-43148 | biostudies-arrayexpress
Project description:Transcriptional profiling of genes expressed in normal parathyroid glands (Normal) and adenomatous parathyroid glands from patients with primary hyperparathyroidism (PHPT). Stratagen Human Refernece RNA, pooled from 10 human cell lines, was used to identify genes, which are specifically expressed or suppressed in parathyroid tissue. Comparison between normal and tumor parathyroids shows genes that might be involved in hyperproliferation and PTH hypersecretion in tumors.
2016-12-01 | GSE83421 | GEO
Project description:The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms in renal epithelial cells downstream of the PTH receptor that control vitamin D metabolism remain unknown. Here we demonstrate that Salt Inducible Kinases (SIKs) control renal 1,25-vit D production downstream of PTH signaling via regulating Cyp27b1 expression. As PTH inhibits the cellular activity of SIKs by cAMP-dependent PKA phosphorylation in bone, we hypothesized that SIKs would also work as an essential mediator of PTH doownstream signaling in kidney, thus regulate vitamin D metabolism. Whole tissue and single cell transcriptomics in kidney demonstrates that both PTH and pharmacologic SIK inhibitors regulate a vitamin D gene module in specific proximal tubule cells. Moreover, small molecule SIK inhibitors directly increase 1,25-vit D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell-derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice show Cyp27b1 upregulation, elevated serum levels of 1,25-vit D, and PTH-independent hypercalcemia. The SIK substrate CRTC2 shows PTH and SIK inhibitor-inducible binding to key Cyp27b1 regulatory enhancers in the kidney, which are also required for SIK inhibitors to increase Cyp27b1 in vivo. Lastly, in a podocyte injury mouse model of chronic kidney disease (CKD) characterized by low 1,25-vit D levels, SIK inhibitor treatment stimulates both renal Cyp27b1 expression and 1,25-vit D production.
2023-01-01 | GSE207800 | GEO
Project description:The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms in renal epithelial cells downstream of the PTH receptor that control vitamin D metabolism remain unknown. Here we demonstrate that Salt Inducible Kinases (SIKs) control renal 1,25-vit D production downstream of PTH signaling via regulating Cyp27b1 expression. As PTH inhibits the cellular activity of SIKs by cAMP-dependent PKA phosphorylation in bone, we hypothesized that SIKs would also work as an essential mediator of PTH doownstream signaling in kidney, thus regulate vitamin D metabolism. Whole tissue and single cell transcriptomics in kidney demonstrates that both PTH and pharmacologic SIK inhibitors regulate a vitamin D gene module in specific proximal tubule cells. Moreover, small molecule SIK inhibitors directly increase 1,25-vit D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell-derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice show Cyp27b1 upregulation, elevated serum levels of 1,25-vit D, and PTH-independent hypercalcemia. The SIK substrate CRTC2 shows PTH and SIK inhibitor-inducible binding to key Cyp27b1 regulatory enhancers in the kidney, which are also required for SIK inhibitors to increase Cyp27b1 in vivo. Lastly, in a podocyte injury mouse model of chronic kidney disease (CKD) characterized by low 1,25-vit D levels, SIK inhibitor treatment stimulates both renal Cyp27b1 expression and 1,25-vit D production.
2023-03-01 | GSE207731 | GEO