Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism

Shilo, Vitali; Levi, Irit Mor‐Yosef; Abel, Roy; Mihailović, Aleksandra; Wasserman, Gilad; Naveh-Many, Tally; Ben‐Dov, Iddo Z.

doi:10.1681/asn.2016050585

Cited by 38 publications

(40 citation statements)

References 50 publications

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“…In addition, we demonstrate that the expression levels of miR-148a are positively correlated with PTH. It has been shown that increased levels of miR-148a in rat parathyroid cultures induce an abnormal PTH secretion; importantly, a specific reduction of such miRNA, by using miR-148a antagomiRs, affected PTH secretion in vivo, thus suggesting an association between miR-148a levels and PTH serum concentration [69]. We can hypothesize that the increased circulating expression of miR-148a may have a broad range of effects, thus potentially modifying the secretion of PTH by targeting parathyroid cells as well.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

Grieco

Cataldo

Ceccarelli

et al. 2018

ncRNA

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Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs. non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

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Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

Grieco

Cataldo

Ceccarelli

et al. 2018

ncRNA

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“…Studies in parathyroid carcinomas identified dysregulated miRNAs when compared to normal parathyroid glands [ 108 , 109 ]. To study the role of miRNAs in SHP, miRNA profiling was performed by deep-sequencing in human parathyroid tissue of end-stage renal disease patients as well as experimental SHP models [ 110 ]. These studies showed that human and rodent parathyroids share similar miRNA profiles.…”

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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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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“…The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism as well as the effect of specific miRNAs on PTH expression indicate their importance for parathyroid function and the development of secondary hyperparathyroidism. 9 MafB contributes to the increased PTH and cyclin D2 expression in secondary hyperparathyroidism. Future studies may link MafB to the other mechanisms that regulate the parathyroid such as the calcium-sensing receptor, the vitamin D receptor, fibroblast growth factor 23, and miRNAs.…”

Section: See Basic Research On Page 54mentioning

confidence: 99%

Transcription factors that determine parathyroid development power PTH expression

Naveh-Many

Silver

2018

Kidney International

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Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism

Cited by 38 publications

References 50 publications

Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Transcription factors that determine parathyroid development power PTH expression

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