Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mapping the Single Cell Transcriptomic Response of Murine Diabetic Kidney Disease to Therapies

ABSTRACT: In this study, we utilized the db/db, uninephrectomy and renin-hypertension mouse model. We compared vehicle to ACE inhibitor, Rosiglitizone, SGLT2 inhibitor, ACEi + Rosiglitizone and ACEi + SGLT2i at two time points (2 days and 2 weeks). We generated snRNA-seq datasets from all groups comprising nearly 1 million cells. Analysis of the resulting atlas revealed that the different medications affected strikingly different cell types. Combination therapy had the largest effects, but these effects were also largely non-overlapping. This study highlights the cellular complexity of diabetic nephropathy and the effects of different classes of therapy. The results support the development of combination therapies since different drug classes target different cell types in kidney.

ORGANISM(S): Mus musculus

PROVIDER: GSE184652 | GEO | 2022/06/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Bulk RNA-seq on mouse model of diabetic nephropathy and in vitro model of SRSF7 knockdown

Project description:In this dataset, we utilized the db/db, uninephrectomy and renin-hypertension mouse model. We performed bulk RNA-seq and compared vehicle to ACE inhibitor, Rosiglitizone, SGLT2 inhibitor, ACEi + Rosiglitizone and ACEi + SGLT2i at two time points (2 days and 2 weeks). To study the mechanism, we also performed bulk RNA-seq on human primary tubular epithelial cells with or without SRSF7 siRNA knockdown.

2022-06-14 | GSE199437 | GEO

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

Analysis of renal protective effects of ARB and SGLT2i at single cell level.

Project description:Angiotensin receptor blockade (ARB) and sodium-glucose co-transporter 2 inhibitor (SGLT2i) have been used as the standard therapy for patients with diabetic kidney disease (DKD). However, how these two drugs possess additive renal protective effects remains unclear. Here, we conducted single cell RNA-sequencing to profile the kidney cell transcriptome of db/db mice treated with vehicle, ARB, SGLT2i, or both drugs and db/m mice. We identified 10 distinct clusters of kidney cells with predominant proximal tubular (PT) cells. We found that ARB has more anti-inflammatory and anti-fibrosis effects while SGLT2i affects more mitochondrial function. We also identified a new PT subcluster which was increased in DKD but reversed by treatments.This new subcluster was also confirmed by Immunostaining of mouse and human kidneys with DKD. Together, our study reveal kidney cell-specific gene signatures in response to ARB and SGLT2i and also identified a new PT subcluster which provides new insight into DKD.

2021-11-05 | GSE181382 | GEO

Transcriptomics of SGLT2-positive early proximal tubule segments in mice: response to type 1 diabetes, SGLT1/2 inhibition or GLP1 receptor agonism

Project description:SGLT2 inhibitors (SGLT2i) and GLP1 receptor (GLP1R) agonists have kidney protective effects. To better understand their molecular effects, RNA sequencing was performed in SGLT2-positive proximal tubule segments isolated by immunostaining-guided laser capture microdissection. Male adult DBA wildtype (WT) and littermate diabetic Akita mice ± Sglt1 knockout (Sglt1-KO) were given vehicle or SGLT2i dapagliflozin (dapa; 10mg/kg diet) for 2 weeks, and other Akita mice received GLP1R agonist semaglutide (sema; 3nmol/[kg body weight*day], s.c.). Dapa (254±11mg/dL) and Sglt1-KO (367±11mg/dL) but not sema (407±44mg/dL) significantly reduced hyperglycemia in Akita mice (480±33mg/dL). The 20,748 detected annotated protein-coding genes included robust enrichment of S1-segment marker genes. Akita showed 198 (~1%) differentially expressed genes vs. WT (DEGs; adjusted p<0.1) including downregulation of anionic transport, unsaturated fatty acid and carboxylic acid metabolism. Dapa changed only 2 genes in WT but restored 43% of DEGs in Akita, including upregulation of lipid metabolic pathway, carboxylic acid metabolism and organic anion transport. In Akita, sema restored ~10% of DEGs, and Sglt1-KO and dapa were synergistic (restored ~61%) possibly involving additive blood glucose effects (193±15mg/dl). Targeted analysis of transporters and channels (t-test p<0.05) revealed that ~10% of 526 detectable transporters and channels were downregulated by Akita, with ~60% restored by dapa. Dapa, dapa+Sglt1-KO and sema also altered Akita-insensitive genes. Among DEGs in Akita, ~30% were unresponsive to any treatment, indicating potential new targets. In conclusion, SGLT2i restored transcription for multiple metabolic pathways and transporters in SGLT2-positive proximal tubule segments in diabetic mice, with a smaller effect also observed for GLP1R agonism.

2024-11-14 | GSE279174 | GEO

Transcriptomic profiling of SGLT2 inhibitor-treated hypertensive rats

Project description:Background: Sodium-glucose co-transporter-2 inhibitor (SGLT2i) compounds are antihyperglycemic medications that may improve cardiovascular disease (CVD) and chronic kidney disease prognosis in patients with diabetes mellitus. Methods: We conducted a detailed RNA-sequencing-based exploration of transcriptomic changes in response to empaglifozin in eight different tissuesfrom a rat model of spontaneous hypertension. Corresponding computational analyses were performed to analyze these data. Results: We discovered that empaglifozin exerts potent transcriptomic effects upon various tissues. Empaglifozin therapy may exert effects upon the kidney by impacting aldosterone-regulated sodium resorption, lyosome. The functional enrichment of DEGs indicated empaglifozin may regulate blood pressure, blood glucose, lipid homeostasis and nervous system in SHR. Consistent with our RNA-Seq findings, following 1-month empaglifozin administration, immunofluorescence staining revealed enhanced renal expression of caveolin-1. Conclusions: These findings offer value as a foundation guiding further exploration regarding the effects associated with SGLT2i therapy in the context of hypertension.

2023-09-06 | GSE206986 | GEO

In utero exposure to therapeutic doses of acetaminophen and ibuprofen accelerates germ cell differentiation in the mouse embryonic testis

Project description:NSAIDs and ACE that affect prostaglandin synthesis are widely used by pregnant women. Epidemiological studies have hypothesized a potential relation of testis dysgenesis syndromes such as cryptorchidism and hypospadias to exposure to these molecules during both the first and the second trimesters of gestation. To decipher whether the embryonic gonads themselves are targets for these molecules, we analysed the impact of precocious in utero exposure to NSAIDs and ACE alone or in combination on the early development of the testis during sex determination, using therapeutic doses similar to those administrated in human medications. We found that in utero exposure to ACE, aspirin or ibuprofen affects the germ cell proliferation in embryonic testis. The whole transcriptome of 13.5 dpc (days post coïtum) treated testis suggests different mechanisms of action of these drugs and a functional interaction between both molecules used in combination, in accelerating the germ cell differentiation. We identified that ACE and ibuprofen exposure through the up-regulation of Dnmt3L expression induces advanced epigenetic reprograming of the germline and enhanced glycogen storage within the testis cords through the activation of extracellular matrix genes expression. In addition, we identified for the first time the prostaglandin production pattern in the embryonic gonad and showed that PGD2, PGE2 and PGI2 were the targets of ACE and NSAIDs drugs. These features might affect the formation and maturation of postnatal testis and secondary reproductive organs leading to male infertility in adult age.

2018-07-01 | GSE89061 | GEO

The effects of SGLT-2 inhibitors canagliflozin on hepatic transcription

Project description:We assessed the change in hepatic transciptional pattern after treatment with SGLT-2 inhibitors canagliflozin in a mice model of diet-induced obesity. Pharmacologic inhibition of the renal sodium/glucose cotransporter-2 induces glycosuria and reduces glycemia. Given that SGLT2 inhibitors (SGLT2i) reduce mortality and CV risk in T2D, improved understanding of molecular mechanisms mediating these metabolic effects is required. Treatment of obese but nondiabetic mice with the SGLT2i canagliflozin (CANA) reduces adiposity, improves glucose tolerance despite reduced plasma insulin, increases plasma ketones, and improves plasma lipid profiles. We utilized an integrated transcriptomic-metabolomics approach to demonstrate that CANA modulates key nutrient-sensing pathways, with activation of AMPK and inhibition of mTOR, independent of insulin or glucagon sensitivity or signaling. Moreover, CANA induces transcriptional reprogramming to activate catabolic pathways, increase fatty acid oxidation, reduce hepatic steatosis and diacylglycerol content, and increase hepatic and plasma levels of FGF21. Taken together, these data demonstrate that SGLT-2 inhibition triggers a fasting-like transcriptional and metabolic paradigm.

2020-04-16 | GSE148702 | GEO

Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

Project description:The precise physiological mechanisms of cardio-renal syndrome are yet to be elucidated. In order to investigate the molecular basis of cardio-renal syndrome, we established a mouse model for cardio-renal syndrome by the combination of abdominal aortic banding and uninephrectomy. Renal function of the cardio-renal syndrome mice was synergistically decreased compared with that of mice that underwent uninephrectomy alone. To investigate the molecules involved in the deterioration renal function in the AbNx mice, we conducted comprehensive gene expression analysis using DNA array by comparing the molecules expressed in the remained kidney of AbNx mice with those of Nx mice. We conducted abdominal aorta banding or sham operation at 0 week, then We conducted uninephrectomy or sham operation at 2 week. We removed these kidney 6week after the uninephrectomy. These RNA samples were purified from the homogenized kidneys.

2012-03-19 | E-GEOD-36591 | biostudies-arrayexpress

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

Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

2012-03-19 | GSE36591 | GEO