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Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels

ABSTRACT: Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels

PROVIDER: PRJNA1034948 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26589953_1.fastq.gz	Fastqsanger.gz
	SRR26589953_2.fastq.gz	Fastqsanger.gz
	SRR26589954_1.fastq.gz	Fastqsanger.gz
	SRR26589954_2.fastq.gz	Fastqsanger.gz
	SRR26589955_1.fastq.gz	Fastqsanger.gz

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Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels [ATAC-seq]

Project description:Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its development at the early phase are highly warranted. Here, we analyzed kidneys from healthy mice, diabetic mice, and diabetic mice treated with the sodium-glucose cotransporter 2 inhibitor dapagliflozin. Our combined method of ATAC and RNA sequencing revealed Csf2rb, Btla, and Isg15 as the key candidate genes associated with hyperglycemia, azotemia, and albuminuria. Their protein levels were altered together with multiple other inflammatory cytokines in the diabetic kidney, which was alleviated by dapagliflozin treatment. Cell culture of immortalized renal tubular cells and macrophages unraveled that dapagliflozin could directly effect on these cells in vitro as an anti-inflammatory agent independent of glucose concentrations. We further proved that dapagliflozin attenuated ischemia/reperfusion-induced chronic kidney injury and renal inflammation in mice. Overall, our data emphasize the importance of inflammatory factors to the pathogenesis of DKD, and provide valuable mechanistic insights into the renoprotective role of dapagliflozin.

2023-11-02 | GSE246763 | GEO

Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels [RNA-seq]

2023-11-02 | GSE246576 | GEO

Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels [RNA-seq]

Project description:Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels [RNA-seq]

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Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels [ATAC-seq]

Project description:Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels [ATAC-seq]

| PRJNA1034577 | ENA

Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases dependent and independent of glucose levels

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

2023-11-02 | GSE246826 | GEO

Dapagliflozin alleviates diabetic kidney disease via HIF1α/HO1 mediated ferroptosis

Project description:Dapagliflozin alleviates diabetic kidney disease via HIF1α/HO1 mediated ferroptosis

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Dapagliflozin alleviates diabetic kidney disease via HIF1α/HO1 mediated ferroptosis

Project description:To investigate the mechanism of the renal protective effects of SGLT2i in diabetic nephropathy, we treated 9-week db/db mice with dapagliflozin and solvent, respectively. This study used m/m mice as control group.We performed gene expression profiling analysis using data obtained from RNA-seq of 3 different groups of mice after 13-week treatment.

2023-05-31 | GSE228727 | GEO

Proximal tubular epithelial specific transcriptomics of diabetic mice treated with dapagliflozin

Project description:We show the proximal tubular specific pathway analysis demonstrating the downregulation of oxidative phosphorylation in dapagliflozin treated db/db mice, a type 2 diabetic model. After 8-week treatment of dapagliflozin for db/db mice having proximal tubule specific tdTomato reporter, tdTomato-positive cells were isolated by FACS. Pathway analysis of RNA sequence of isolated tubular epithelia revealed that oxidative phosphorylation was downregulated in dapagliflozin-treated mice. However, depletion of renal tissue ATP content in db/db mice was ameliorated by dapagliflozin administration. Pimonidazole staining demonstrated that renal cortical tissue hypoxia was noted in db/db mice, which was improved by dapagliflozin administration. These findings suggest that dapagliflozin can ameliorated the excessive oxygen and ATP consumption and subsequent tissue hypoxia in diabetic kidney, which may explain, in part, the responsible mechanisms of renoprotecitive effect by dapagliflozin.

2022-09-28 | GSE185801 | GEO

Dapagliflozin protects against chronic heart failure in mice via inhibiting macrophage-mediated inflammation, independent of SGLT2 [RNA-Seq]

Project description:The specific mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitor in heart failure (HF) needs to be elucidated. In this study, we use SGLT2 global knockout (SGLT2-KO) mice to assess the mechanism of SGLT2 inhibitor on HF. Dapagliflozin ameliorates both myocardial infarction (MI)-and transverse aortic constriction (TAC) -induced HF. Global SGLT2-deficiency doesn’t exert protection against adverse remodeling in both MI- and TAC-induced HF models. Dapagliflozin blurs MI- and TAC-induced HF phenotypes in SGLT2-KO mice. Dapagliflozin causes major changes in cardiac fibrosis and inflammation. Based on single-cell RNA sequencing dapagliflozin causes significant differences in the gene expression profile of macrophages and fibroblasts. Moreover, dapagliflozin directly inhibites macrophage inflammation, thereby suppressing cardiac fibroblasts activation. The cardio-protection of dapagliflozin is blurred in mice treated with a C-C chemokine receptor type 2 (CCR2) antagonist. Taken together the protective effects of dapagliflozin against HF are independent of SGLT2, macrophage inhibition is the main target of dapagliflozin against HF.

2023-11-14 | GSE247062 | GEO

HK-2 cell cultured with normal glucose, high glucose, dapagliflozin, metformin and vildagliptin

Project description:To investigate the differential expressed circRNAs, and even their biological functions in human proximal tubular epithelial (HK-2) cells induced by normal glucose, high levels of glucose and treatment of dapagliflozin, metformin and vildagliptin.

2022-04-05 | GSE179226 | GEO

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