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

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

PROVIDER: PRJNA857086 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20063712.fastq.gz	Fastqsanger.gz
	SRR20063713.fastq.gz	Fastqsanger.gz
	SRR20063714.fastq.gz	Fastqsanger.gz
	SRR20063715.fastq.gz	Fastqsanger.gz
	SRR20063716.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

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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

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

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

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 [SK]

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

| PRJNA856978 | ENA

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

2023-03-01 | GSE207733 | GEO

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

2023-03-01 | GSE207731 | GEO

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

Project description:The underling mechanism used by PTH to promote 1,25-vitamin D synthesis remains unknown. Here, we demonstrate that Salt Inducible Kinases (SIK) inhibitors drive renal 1,25-vitamin D production, as PTH inhibits SIK cellular activity by cAMP-dependent PKA phosphorylation. Although there are some evidence that PTH increases Cyp27b1 in proximal tubule epithelial cells, this has not been explored/confirmed using next generation sequencing. Thus, we are interested in identifying cell populations that are responsible for PTH- or SIK-inhibition induced Cyp27b1 increase.

2022-11-15 | GSE213316 | 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

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

2023-03-01 | GSE207734 | GEO