Renin-angiotensin system inhibition reverses the altered triacylglycerol metabolic network in diabetic kidney disease
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ABSTRACT:
PROVIDER: PRJNA594364 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10611900_1.fastq.gz | Fastqsanger.gz | |||
| SRR10611900_2.fastq.gz | Fastqsanger.gz | |||
| SRR10611901_1.fastq.gz | Fastqsanger.gz | |||
| SRR10611901_2.fastq.gz | Fastqsanger.gz | |||
| SRR10611902_1.fastq.gz | Fastqsanger.gz |
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Project description:Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). To identify individual lipids and lipid networks that may be involved in DKD progression, we performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with nondiabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network. Keywords: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). To identify individual lipids and lipid networks that may be involved in DKD progression, we performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.
2022-07-08 | GSE141680 | GEO
Project description:LC-MS/MS Proteomics was performed to determine proteomic differences between colon adenocarcinoma (CA) tissues and patient-matched normal colon tissues, CA-derived primary cell lines and NC-derived primary cells, and between LGCA tissues and cell lines and HGCA tissues and cell lines. Biological processes which may link the renin-angiotensin system and CA were investigated, revealing enrichment of various signalling pathways that may play roles in CA onset and progression directly or via the renin-angiotensin system.
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Project description:ObjectiveDyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). Determining the changes in individual lipids and lipid networks across a spectrum of DKD severity may identify lipids that are pathogenic to DKD progression.MethodsWe performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model.ResultsOf the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition.ConclusionsIn addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.
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Project description:Regulated endocrine specific protein 18 (Resp18), expression has been specifically located in a series of tissues and cell types however the exact cellular function is unknown. In previous studies we have showed that a targeted disruption of Resp18 in Dahl SS rats (Resp18mutant) resulted in higher blood pressure (BP), increased renal fibrosis, and decreased survival rate on a long term (6-week) 2% high salt (HS) diet treatment compared with wild type SS rats. In the current study we studied whether a short term (1 week) exposure to HS diet shows a similar effect in Resp18mutant rats. Furthermore, previously we have shown that in addition to BP phenotype Resp18mutant rats have demonstrated deteriorative kidney phenotype evident through renal fibrosis, protein urea and protein cast formation. Based on this background we conducted BP study and performed transcriptomic profiling of the kidney after one-week exposure to HS diet treatment. Through radio-telemetry procedure, we found that the systolic BP was increased in the Resp18mutant rats compared with SS rats even with short term HS diet exposure. Therefore, we sought out to investigate if there was any alteration in the transcriptomic response by HS diet treatment in the Resp18mutant rat kidneys. Using RNA sequencing approach, we found that Resp18mutant rats showed a differential expression of 25 genes of which one was an upregulation of Ren. We confirmed the upregulation of Ren and other differentially expressed genes via qRT-PCR analysis. Upon KEGG pathway enrichment we found that the Resp18mutant rat showed upregulation in the renin angiotensin system (RAAS), and renin secretion pathway. Furthermore, the renin activity is found to be higher in Resp18mutant rats serum compared with SS rats. Therefore, these observations demonstrate that upon disruption of Resp18 gene in SS rats associated with the increase in renin secretion and thus increase BP.
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