Perirenal Adipose Afferent Nerves Sustain Pathological High Blood Pressure
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA674829 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12992478_1.fastq.gz | Fastqsanger.gz | |||
| SRR12992478_2.fastq.gz | Fastqsanger.gz | |||
| SRR12992479_1.fastq.gz | Fastqsanger.gz | |||
| SRR12992479_2.fastq.gz | Fastqsanger.gz | |||
| SRR12992480_1.fastq.gz | Fastqsanger.gz |
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Project description:Hypertension is a pathological condition of persistent high blood pressure (BP) of which the underlying mechanisms remain largely obscure. Here, we show that the afferent nerves in perirenal adipose tissue are a regulatory site in triggering and maintaining pathological high BP, without affecting physiological BP. Bilateral perirenal adipose tissue (PRAT) ablation leads to a long-term and effective reduction of BP in spontaneous hypertensive rats (SHR) and high fat and high salt diet fed rats, but has no effect on normal BP in control Wistar-Kyoto or control SD rats. Moreover, gain- and loss-of-function studies show that augmented activities of L1-L2 dorsal root ganglia (DRG) neurons are responsible for hypertension in SHR. Further, L1-L2 DRG neuron transcriptomics uncovers significant changes in neuron development, remodeling, and plasticity. Importantly, calcitonin gene-related peptide (CGRP), a systemic vasodilator, is induced after PRAT ablation. We went on to show that CGRP antagonist blocks the BP-lowering effect of PRAT ablation. CGRP is therefore a key endogenous suppressor of hypertension that is sequestered by anti-hypertensive PRAT in SHRs. Taken together, we identify PRAT afferent nerves as a pathological node of hypertension that sustains high BP via suppressing CGRP, thereby providing a therapeutic target to tackle primary hypertension.
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Project description:Analysis of perirenal adipose tissue from healthy kidney donors (age 44±9 years, BMI 25.8±3.3 kg/m2, mean±SD). The samples were taken bylaparoscopic technique beneath the incision plane that was created in the renal fascia (Greotas fascia) close to the renal vein. Ten samples of human perirenal adipose tissue
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Project description:Primary afferent collateral sprouting (PACS) is a process whereby non-injured primary afferent neurons respond to some stimulus by extending new branches from existing axons. In the model used here (spared dermatome), the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity. Investigations of gene expression changes associated with PACS can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatment for spinal cord injury to promote functional recovery. In this study, we sought to identify gene expression changes in PACS using 20 Affymetrix Rat Genome 230 2.0 microarrays. The experiments were designed to discover global gene expression changes in non-injured DRG neurons undergoing PACS. T11 DRG neurons remained intact and undergo PACS after the cutaneous nerves of the adjacent segments (T9, T10, T12, and T13) were injured and regeneration of those injured nerves prevented by ligation. Thus, the T9, T10, T12, and T13 dermatomes were denervated, but the T11 dermatome remained intact. Axons of the T11dermatome (and thus housed in the T11 dorsal root ganglion (DRG)), extended new branches to innervate the T9, T10, T12, and T13 dermatomes. N.B.: This is NOT a spared root experiment. ALL spinal roots were non-injured. Peripheral nerves were used.
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Project description:The aim of this study was to perform a comparative analysis of the perirenal fat transcriptomes of suckling lambs from two breeds with different growth and carcass characteristics. The perirenal fat tissue from 14 suckling lambs (Assaf= 8, Churra= 6) was used for the RNA-Seq analysis. The functional enrichment analysis of the 670 highly expressed genes (>150 fragments per kilobase of exon per million fragments mapped) in the perirenal fat transcriptome of both breeds revealed that the majority of these genes were involved in energy processes. The differential expression analysis performed identified 373 differentially expressed genes (DEGs) between the two compared breeds. In Assaf lambs, DEGs were enriched in Gene Ontology (GO) biological processes related to fatty-acid oxidation, while in Churra lambs, the majority of the significantly enriched GO terms were related to cholesterol synthesis, which suggests that upregulated DEGs in Assaf lambs are implicated in fat burning, while the Churra upregulated DEGs are linked to fat accumulation.
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Project description:Primary afferent collateral sprouting (PACS) is a process whereby non-injured primary afferent neurons respond to some stimulus by extending new branches from existing axons. In the model used here (spared dermatome), the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity. Investigations of gene expression changes associated with PACS can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatment for spinal cord injury to promote functional recovery. In this study, we sought to identify gene expression changes in PACS using 20 Affymetrix Rat Genome 230 2.0 microarrays. The experiments were designed to discover global gene expression changes in non-injured DRG neurons undergoing PACS. T11 DRG neurons remained intact and undergo PACS after the cutaneous nerves of the adjacent segments (T9, T10, T12, and T13) were injured and regeneration of those injured nerves prevented by ligation. Thus, the T9, T10, T12, and T13 dermatomes were denervated, but the T11 dermatome remained intact. Axons of the T11dermatome (and thus housed in the T11 dorsal root ganglion (DRG)), extended new branches to innervate the T9, T10, T12, and T13 dermatomes. N.B.: This is NOT a spared root experiment. ALL spinal roots were non-injured. Peripheral nerves were used. A total of 20 Affymetrix Rat Genome 230 2.0 microarrays were analyzed: six naïve controls, seven replicates at day 7 post-surgery (presumed to represent an â??initiation phaseâ??), and seven replicates at day 14 post-surgery (presumed to represent a â??maintenance phaseâ??). DRGs were NOT pooled onto microarrays. Each animal had its own microarray with T11 DRG sample which underwent 2-round amplification. After quality control analysis, one of the naïve control microarrays was removed from further analysis.
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