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RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus

ABSTRACT: RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus

PROVIDER: PRJNA480113 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7495600_1.fastq.gz	Fastqsanger.gz
	SRR7495600_2.fastq.gz	Fastqsanger.gz
	SRR7495610_1.fastq.gz	Fastqsanger.gz
	SRR7495610_2.fastq.gz	Fastqsanger.gz
	SRR7495620_1.fastq.gz	Fastqsanger.gz

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RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus

Project description:Purpose: Lithium salts, used for treatment of bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI), limiting therapeutic success. NDI is associated with loss of expression of the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use the methods of systems biology in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Methods: We carried out RNA-sequencing in cortical CDs microdissected from rats treated with lithium for 12-72 hours (vs. time controls). Administration of anti-inflammatory doses of dexamethasone to lithium-treated rats countered the loss of aquaporin-2 protein. Protein mass spectrometry in microdissected cortical CDs provided corroborative evidence, but also identified decreased abundance of several anti-oxidant proteins. Cortical thick ascending limbs of Henle were also microdissected for RNA-Seq at 72 hrs. We carried out RNA-Seq for 2-3 CCD sample per rat (1 lithium-treated rat versus 1 control at 12, 24, 36 hrs). Results and conclusion: Integration of new data with prior data about lithium effects at a molecular level leads to a signaling model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 gene transcription.

2019-04-04 | GSE116760 | GEO

RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus.

Project description:Lithium salts, used for treating bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI) thereby limiting therapeutic success. NDI is associated with loss of expression of the gene coding for the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use systems biology methods in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts (CCDs) of rats after 72 hours without or with initiation of lithium chloride administration. Transcriptome-wide changes in mRNA abundances were mapped to gene sets associated with curated canonical signaling pathways, showing evidence for activation of NF-κB signaling with induction of genes coding for multiple chemokines and most components of the Major Histocompatibility Complex Class I antigen-presenting complex. Administration of anti-inflammatory doses of dexamethasone to lithium chloride-treated rats countered the loss of aquaporin-2. RNA-Seq also confirmed prior evidence of a shift from quiescence into the cell cycle with arrest. Time course studies demonstrated an early (12 hour) increase in multiple immediate early response genes including several transcription factors. Protein mass spectrometry in microdissected CCDs provided corroborative evidence and identified decreased abundance of several anti-oxidant proteins. Thus, in the context of prior observations, our study can be best explained by a model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 transcription.

| S-EPMC6650374 | biostudies-literature

Signaling Mechanisms in Initiation of Lithium-Induced Nephrogenic Diabetes Insipidus

Project description:Lithium treatment is commonly used to treat bipolar disorder. However, this treatment disrupts kidney fuctionality. We used microdissected cortical collecting ducts to study proteomics and ultimately discover what changes occur in protein expression after 72-hr lithium treatment.

2019-07-01 | PXD010118 | Pride

Transcriptome Changes of Microdissected Kidney Tubules triggered by Unilateral Nephrectomy [RNA-seq]

Project description:Purpose: Experiments were done in mice undergoing unilateral nephrectomy (UNx) and sham nephrectomy. At specific time points (24 hours and 72 hours) after surgery, the earliest first portion of the kidney proximal tubule (PT-S1) and the cortical collecting duct (CCD) were manually micro-dissected and utilized for transcriptomic analysis by single-tubule small sample RNA-Seq. Methods: We carried out RNA-sequencing in microdissected ealiest portion of proximal tubules (PT-S1) or cortical collecting duct (CCD) from mice with or without (sham) unilateral nephrectomy (UNx). Each group (Sham or UNx) has 3-5 biological replicates. Results and conclusion: RNA-Seq in microdissected PT-S1 at 24 hours showed that peroxisome proliferator-activated receptor alpha (PPARα) target genes were strongly upregulated. RNA-Seq in microdissected PT-S1 at 72 hours showed that cell cycle related genes were strongly upregulated. RNA-Seq in microdissected CCD at both 24 hours and 72 hours showed that cell cycle related genes were strongly upregulated.

2022-08-14 | GSE211021 | GEO

Transcriptome Changes of Microdissected Kidney Tubules triggered by Unilateral Nephrectomy [RNA-seq]

Project description:Transcriptome Changes of Microdissected Kidney Tubules triggered by Unilateral Nephrectomy [RNA-seq]

| PRJNA868702 | ENA

Shotgun proteomics analysis of single human tubules

Project description:We analyzed microdissected single tubules from human with shotgun proteomics.

2018-06-28 | PXD006897 | Pride

Gene expression profiles in isolated proximal tubules and whole kidneys of rats after cisplatin-administration

Project description:To clarify the effects of cisplatin (cis-diamminedichloroplatinum II, CDDP) on the gene expression profiles in renal proximal tubules, microarray analyses were carried out using total RNA samples isolated from microdissected proximal tubules and whole kidneys. The molecular events underlying acute kidney injury (AKI) in the proximal tubules of rats with cisplatin-induced nephrotoxicity were successfully clarified with 17,000 transcripts.

2013-12-24 | GSE37133 | GEO

Gene expression profiles in isolated proximal tubules and whole kidneys of rats after cisplatin-administration

2013-12-24 | E-GEOD-37133 | biostudies-arrayexpress

Lithium treatment and human hippocampal neurogenesis

Project description:Lithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.75 mM) and high (2.25 mM) doses of lithium on human hippocampal progenitor cells and used immunocytochemistry to investigate the effects of lithium on cell parameters implicated in neurogenesis. Corresponding RNA-sequencing and gene-set enrichment analyses were used to evaluate whether genes affected by lithium in our model overlap with those regulating the volume of specific layers of the dentate gyrus. We observed that high-dose lithium treatment in human hippocampal progenitors increased the generation of neuroblasts (P ≤ 0.01), neurons (P ≤ 0.01), and glia (P ≤ 0.001), alongside the expression of genes which regulate the volume of the molecular layer of the dentate gyrus. This study provides empirical support that adult hippocampal neurogenesis and gliogenesis are mechanisms that could contribute to the effects of lithium on human hippocampal volume.

2021-09-30 | GSE184930 | GEO

Effects of amiloride in lithium induced kidney interstitial fibrosis

Project description:Purpose: The goal of this study is to understand the role of co-administred amiloride. This was derived through RNAseq of kidney cortex and determining differential genes in response to lithium, lithium+amiloride and control at 14 days, 28 days and 6 months. Methods: RNAseq of kidney cortex treated with either lithium alone, lithium+amiloride or control. Deseq2 was performed using contrast argument with Wald test to identify significant differentially expression genes at each time point individually. Result & Conclusion: Co-administration with amiloride at all time points contributed in the reduction of inflammation and fibrosis caused by lithium.

2022-08-31 | GSE178950 | GEO

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