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RNA-seq from the kidney of 50-weeks-old db/db mice that underwent 40 weeks atorvastatin treatment

ABSTRACT: Statin play an important role in the treatment of diabetic nephropathy (DN). In recent years, increasing attention has been given to the relationship between statin and insulin resistance, but many randomized controlled trial (RCT) studies confirm that the therapeutic effect of statin on DN is more beneficial than harmful. However, further confirmation of whether the beneficial effects of long-term statin administration on DN still outweigh the detrimental effects is needed. In the current study, we found that long-term statin administration may exacerbate insulin resistance, interfere with glucose and lipid metabolism, lead to renal cell apoptosis, inflammation and severe renal fibrosis, and ultimately decrease renal function. Mechanistically,Through RNA seq analysis, we found that long-term statin administration affects lipid metabolism and exacerbates inflammation and fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE196701 | GEO | 2022/05/15

REPOSITORIES: GEO

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Project description:Patients with combined heart and renal failure, also termed the cardiorenal syndrome (CRS), have high cardiovascular morbidity and mortality. Several key connectors between heart and kidney have been recognized, such as oxidative stress, inflammation, the renin-angiotensin system and the sympathetic nervous system. Monocytes are key players in the development of atherosclerosis and may act as a biosensor to detect changes in the systemic environment. Anemia, which occurs frequently in CRS, is partly due to an absolute and/or relative erythropoietin (EPO) deficiency. Until now, EPO treatment has largely been used to treat (renal) anemia, but recent research also showed beneficial non-hematopoietic effects such as anti-inflammatory and anti-oxidative capacities. The hypothesis of the present study was that monocyte gene expression profiles of cardiorenal patients compared to healthy controls reflect the systemic nature of CRS and are responsive to short-term treatment with Epo. The first aim was to investigate whether this short term treatment revealed non-hematopoietic EPO effects. The second aim was to address whether EPO dampens expression of genes involved in inflammation and oxidative stress. Given the variable response to EPO, the third aim was to test whether baseline gene expression profiles or the acute gene expression modulation by EPO are associated with EPO resistance. This study was part of a larger clinical trial in which hematopoietic and non-hematopoietic effects of EPO treatment for short and long term are assessed in CRS patients. Therefore, patients were randomized into 3 groups: (1) EPO, patients are kept on baseline low hemoglobin levels by phlebotomy for 6 months; (2) EPO, patients may rise in hemoglobin levels to defined maximum for 6 months; (3) No EPO. This gene expression analysis is focussed on EPO's short-term (2wk) effects in a subset of included patients. Group (1) and (2) were grouped for analysis, since both groups received EPO and no phlebotomy had been performed in the first 2 weeks. Monocytes were positively isolated from peripheral whole blood with CD14+ immunomagnetic beads. Total RNA was isolated and prepared for genome wide analyses using Illumina HumanRef8 V3.0 Beadchips. In total, 48 arrays were analyzed including 12 healthy controls, 18 CRS patients at baseline and 2 weeks after study enrollment. Twelve out of 18 patients received EPO during the two weeks. The supplementary file 'GSE17582_non-normalized_data.txt' contains non-normalized data for Samples GSM438053-GSM438100.

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RNA-seq from the kidney of 50-weeks-old db/db mice that underwent 40 weeks atorvastatin treatment

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