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A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis [SK]

ABSTRACT: A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis [SK]

PROVIDER: PRJNA856978 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20046902.fastq.gz	Fastqsanger.gz
	SRR20046903.fastq.gz	Fastqsanger.gz
	SRR20046904.fastq.gz	Fastqsanger.gz
	SRR20046905.fastq.gz	Fastqsanger.gz
	SRR20046906.fastq.gz	Fastqsanger.gz

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A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

Project description:A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

| PRJNA857086 | ENA

A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

Project description:A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

| PRJNA856970 | ENA

A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

Project description:A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

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A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis [SK]

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 | GSE207733 | GEO

A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis [SIK]

Project description:A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis [SIK]

| PRJNA856899 | ENA

A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

2023-01-01 | GSE207800 | GEO

Parathyroid hormone exacerbates pulmonary hypertension through hypoxia-induced parathyroid hormone receptor upregulation.

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

A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis [SIK]

2023-03-01 | GSE207731 | GEO

Genes regulated by high calcium medium in parathyroid tissue explants from patients with primary hyperparathyroidism

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

A Parathyroid Hormone/Salt Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-01 | GSE207734 | GEO