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| Status |
Public on Mar 21, 2017 |
| Title |
microRNA profiling in normal and hyperplastic human and murine parathyroid glands |
| Organisms |
Homo sapiens; Mus musculus; Rattus norvegicus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Between 2 and 6 biological replicates are studied in each parathyroid control and hyperplastic group in humans and several different murine models (normal rats, short-, intermediate- and long-term uremia in rats, hypocalcemia in rats and normal mice), and in additional several human thyroid specimens; altogether 55 samples.
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| Web link |
http://jasn.asnjournals.org/content/early/2017/03/14/ASN.2016050585.long
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| Contributor(s) |
Shilo V, Levi IM, Naveh-Many T, Ben-Dov IZ |
| Citation(s) |
28298326 |
| Submission date |
Mar 30, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Iddo Z. Ben-Dov |
| E-mail(s) |
iddo@hadassah.org.il
|
| Phone |
+97226776881
|
| Organization name |
Hadassah Medical Center
|
| Department |
Nephrology and Hypertension
|
| Lab |
Laboratory of Medical Transcriptomics
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| Street address |
Ein Kerem
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| City |
Jerusalem |
| ZIP/Postal code |
91120 |
| Country |
Israel |
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| Platforms (4)
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| GPL10669 |
Illumina Genome Analyzer IIx (Rattus norvegicus) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (55)
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| Relations |
| BioProject |
PRJNA316852 |
| SRA |
SRP072567 |
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