Unknown,Transcriptomics,Genomics,Proteomics

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Expression data of embryonic kidney from MWF E15.5 and SHR 16.0 rats

ABSTRACT: Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter (MWF) rat that exhibits a congenital nephron deficit and renal failure with age. We performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF E15.5 with stage-matched spontaneously hypertensive rats (SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (FC >+1.5 or <-1.5, FDR<0.05). 8 samples were analyzed, n=4 per group

ORGANISM(S): Rattus norvegicus

SUBMITTER: Reinhold Kreutz

PROVIDER: E-GEOD-66079 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Neural progenitor cells (NPCs) have regenerative capabilities that are activated during inflammation. By measuring the global transcriptome and performing functional studies, we aimed at elucidating if and how NPCs from the non-germinal niche of the spinal cord differ from germinal niche NPCs, here represented by the subventricular zone (SVZ) NPCs. Moreover, we investigated how these cells are affected by chronic inflammation modeled by Experimental Autoimmune Encephalomyelitis (EAE). NPCs were isolated and propagated from the SVZ and cervical, thoracic and caudal regions of the spinal cord from healthy rats and rats subjected to EAE. Using Affymetrix microarray analyses, the global transcriptome was measured in the different NPC populations both in undifferentiated and differentiated cultures. These analyses were paralleled by differentiation studies and quantitative RT-PCR of differentiation-specific genes. In NPCs isolated from healthy rats, transcriptional and functional analyses revealed a higher neurogenic potential in SVZ-derived NPCs compared to spinal cord NPCs. The neurogenicity of spinal cord NPCs was increased by exposure to the inflammatory environment. Concurrently, their gliogenicity was decreased which was supported by a decreased expression of glial differentiation signature genes and related signaling pathways. Differentiation analyses showed that spinal cord NPCs from EAE rats generated fewer oligodendrocytes and astrocytes than NPCs isolated from healthy controls. 54 samples were analysed. The transcriptome of NPCs isolated from healthy rats or rats with EAE was measured. The NPCs were isolated from the SVZ and the cervical, thoracic and caudal parts of the spinal cord. Pair wise student t-test analysis between the 3 EAE replicates and naive controls for each respective tissue type was performed. Genes with a signal value above the cut-off of 50 and with FDR M-bM-^IM-$ 5% and a foldchange of M-bM-^IM-%1.2 or M-bM-^IM-$-1.2 were selected for further analysis.

Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.

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Expression data of embryonic kidney from MWF E15.5 and SHR 16.0 rats

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