MicroRNA profiling in normal and hyperplastic human and murine parathyroid glands
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE79727
PROVIDER: PRJNA316852 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3313340.fastq.gz | Fastqsanger.gz | |||
| SRR3313350.fastq.gz | Fastqsanger.gz | |||
| SRR3313360.fastq.gz | Fastqsanger.gz | |||
| SRR3313370.fastq.gz | Fastqsanger.gz | |||
| SRR3313380.fastq.gz | Fastqsanger.gz |
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Project description:The mechanisms of chronic kidney disease-associated secondary hyperparathyroidism are partially understood. In this project we aimed to gain new information and propose research hypotheses by proteome and phosphoproteome profiling of normal and hyperplastic rat parathyroid glands. Glands were microdissected from rats on normal control diet or CKD-inducing high adenine diet enriched with phosphorus to produce secondary hyperparathyroidism. Protein extracts were pooled from 4 glands (2 rats) for proteome profiling (3 normal and 3 CKD pools), and from 12 glands (6 rats) for phosphoproteome profiling (2 normal and 2 CKD pools).
2022-06-28 | PXD029368 | Pride
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:The mechanisms of chronic kidney disease-associated secondary hyperparathyroidism are partially understood. In this project we aimed to gain new information and propose research hypotheses by proteome and phosphoproteome profiling of normal and hyperplastic rat parathyroid glands. Glands were microdissected from rats on normal control diet or CKD-inducing high adenine diet enriched with phosphorus to produce secondary hyperparathyroidism. Protein extracts were pooled from 12 glands (6 rats) for phosphoproteome profiling (3 normal and 3 CKD pools).
2022-06-28 | PXD029401 | Pride
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:Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The understanding of parathyroid hyperplastic growth and the development of tracers for imaging and treatment could benefit from in vitro models. Therefore, we aim to establish stem cell-derived three-dimensional organoids representing human parathyroid tissue in vitro. Patient-derived hyperplastic parathyroid tissue was dispersed and parathyroid organoids (PTO) were cultured, characterized by immunofluorescence, and RNA-sequencing was performed. Functional PTO testing was performed by calcium-response measurements, drug screening, PET (11C-methionine) and SPECT-tracer (99mTc-sestamibi) validation. PTO in vitro self-renewal potential was assessed to show the presence of putative stem cells. RNA-sequencing confirms that PTO phenocopy hyperplastic parathyroid tissue. Exposure to increasing calcium concentrations and to PTH-lowering drugs, resulted in a significantly reduced PTH excretion. Next to this, the PTO showed specific binding of 11C-methionine to the targeted receptor. Additionally, when organoids were incubated with 99mTc-sestamibi, we observed a higher uptake in PTOs from patients with a positive scan compared to patients with a negative scan. In conclusion, we present a patient-derived PTO culture, that recapitulates the originating tissue on gene and protein expression and functionality. We demonstrate the potential of PTOs for physiology studies and therapeutic target and tracer discovery.
2022-02-28 | GSE197445 | GEO
Project description:Here we used proteomic technique to characterize oxyphil cells by comparing the differences between chief and oxyphil cell nodules of parathyroid glands in uremic patients.
2021-11-16 | PXD029762 |
Project description:Primary hyperparathyroidism is a common endocrine disorder frequently affecting postmenopausal women. In this study we have investigated expression of the prolactin receptor (PRLr) in a panel of 37 sporadic parathyroid tumours, as well as functionality in vitro in cultured parathyroid tumour cells. High levels of the prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues as compared to other reference tissues and breast cancer cells. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours PRLr immunoreactivity was observed in cytoplasm in all cases and in addition in the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim PRLr was expressed in cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells prolactin stimulation was associated with transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signaling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumors was significantly inversely correlated with plasma total Ca2+ levels. In conclusion, the prolactin receptor was found highly abundant in human parathyroid gland, parathyroid tumours, correlated with patient Ca2+ levels and functionally responsive to physiological levels of prolactin. These findings suggest a role for the prolactin receptor in human parathyroid adenomas.
2012-05-01 | GSE32387 | GEO
Project description:Studies on human parathyroid tissue are often limited to adenomatous tissue due to difficulty obtaining healthy tissue. We obtained nonhuman primate parathyroids to provide a suitable alternative for sequencing analysis that would bear the closest semblance to human organs as possible. We analyzed four M. mulatta normal parathyroid specimens to that show a continuous trajectory of cell states comprising the normal adult parathyroid. We calculated the predicted pseudotime progression based on transcriptomic signatures that were reflective of repopulating progenitors, progressing to chief cells, and ultimately oxyphils, and clustered genes based on their expression dynamics along this axis. As a comparator, we histologically characterized and sequenced four human adenomas with varying oxyphil and chief cell abundance to highlight similarities and differences to normal parathyroid cell expression dynamics. We noted abundant RARRES2 transcripts that were detected in both human adenoma and normal primate parathyroid cells, and provided co-immunostaining validation of Chemerin presence in PTH-expressing cells, which could play a previously unrecognized role in parathyroid endocrine function.
2024-03-12 | GSE233962 | GEO
Project description:Primary hyperparathyroidism is a common endocrine disorder frequently affecting postmenopausal women. In this study we have investigated expression of the prolactin receptor (PRLr) in a panel of 37 sporadic parathyroid tumours, as well as functionality in vitro in cultured parathyroid tumour cells. High levels of the prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues as compared to other reference tissues and breast cancer cells. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours PRLr immunoreactivity was observed in cytoplasm in all cases and in addition in the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim PRLr was expressed in cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells prolactin stimulation was associated with transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signaling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumors was significantly inversely correlated with plasma total Ca2+ levels. In conclusion, the prolactin receptor was found highly abundant in human parathyroid gland, parathyroid tumours, correlated with patient Ca2+ levels and functionally responsive to physiological levels of prolactin. These findings suggest a role for the prolactin receptor in human parathyroid adenomas. Expression profiling was done in parathyroid adenomas subjected to prolactin treatment in culture. In addition, corresponding paraffin sections were obtained for verification of PRLr expression by immunohistochemistry. 200 mg/L prolactin (recombinant humanM-BM- prolactin, Cat. No. JM-4687-50, MBL Woburn, MA) was added to 1M-CM-^W 10^6 attached parathyroid tumour cells. Cells were harvested using RNAlater (QIAGEN) and homogenized with QIAshredder for RNA extraction after 3 h and 24 h in culture, respectively. Negative controls were collected in parallel with each case at the same time points. RNA was extracted using QIA Cube, and quality assessed with Bioanalyser and Nanodrop. Expression array profiling and data analysis was done at the KI core facility Bioinformatics and Expression Analysis (BEA, Novum, Huddinge) using the Affymetrix platform and the TITAN ST 1.1 array. A total of 16 samples were analysed including 4 parathyroid adenomas cultured for 3 h or 24 h in the presence of prolactin plus control samples cultured in parallel without prolactin.
2012-04-30 | E-GEOD-32387 | biostudies-arrayexpress
Project description:To investigate genes modulated in the parathyroid glands by calcium, expression levels of mRNA for all genes expressed in parathyroid tissue explants (PTEs) obtained from patients with primary hyperparathyroidism (I-HPT) were analyzed by oligo-DNA microarray. PTEs obtained from 4 patients with I-HPT were precultured in normocalcemic medium (Ca++ 1.0-1.1 mM) for 7 days and then cultured in hypocalcemic medium (Ca++ 0.60 mM) or hypercalcemic (Ca++ 1.60 mM) medium for an additional 7 days. As expected, expression levels of mRNA for PTH and chromogranin A were decreased to less than 50% in hypercalcemic medium. Furthermore, oligo-DNA microarray analyses followed by GeneSpring GX analyses revealed that 7 genes were up-regulated by more than 2-fold and more than 30 genes were down-regulated by more than 1/2 in PTEs obtained from patients with I-HPT. Interestingly, 9 of these genes (up-regulated genes: chemokine ligand 8[CCL8], multiple C2 domain and transmembrane region protein 1 [MCTP1]; down-regulated genes: matrix metallopeptidase-9 [MMP9], B-box and SPRY domain-containing protein [BSPRY], nitric oxide synthase 2A [NOS2A], parathyroid hormone [PTH], cartilage acidic protein 1 [CRTAC1], chromogranin A [CHGA], and fibrin 1 [FBLN1]) were involved in calcium metabolism or calcium-signaling pathways in the parathyroid tissue. Unexpectedly, however, the expression level of mRNA for alpha-klotho was variable, and it was not constantly decreased in hypercalcemic medium under the present experimental conditions. Although it was not possible to use normal parathyroid tissue, this is the first reported study to have investigated the expression levels of mRNA for all genes in human parathyroid adenomas that are modulated by high calcium concentration in organ culture.
2009-10-23 | GSE18689 | GEO