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Lupus nephritis serum induces changes in gene expression in human glomerular endothelial cells, which is modulated by L-sepiapterin: Implications for redox-mediated endothelial dysfunction

GSE296560 Homo sapiens (human) RNA-seq (gene expression) 19 samples Submitted 2025/06/18 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 19 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
19 samples: 5 × Healthy Control vs 5 × LN flare vs 5 × LN flare + LSep vs 4 × LN remissionGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Lupus nephritis serum induces changes in gene expression in human glomerular endothelial cells, which is modulated by L-sepiapterin: implications for redox-mediated endothelial dysfunctionLupus science & medicine · 2025
Summary (written by the submitters)
Lupus nephritis (LN) is characterized by renal endothelial dysfunction, which contributes to progressive kidney injury. Endothelial nitric oxide synthase (eNOS) plays a modulating role in LN, as genetic ablation of the eNOS enzyme worsens disease. Serum from patients with active LN induces uncoupling of eNOS homodimers, leading to superoxide (SO) rather than nitric oxide (NO) production by eNOS.
Read the full summary ↓
This uncoupling is reversed with L-sepiapterin (L-Sep). This study was designed to further examine changes in gene expression in glomerular endothelial cells induced by LN serum and whether treatment with L-Sep can ameliorate these changes. Methods Primary human renal glomerular endothelial cells (HRGECs) were cultured with serum from non-lupus controls (HC), LN patients during remission (LN rem), or LN patients during flare (LN flare) with and without L-Sep. Bulk RNA sequencing was performed on RNA isolated from cultured cells. Differential gene expression was determined, and pathway and gene enrichment analyses were performed on differentially expressed genes. Results L-Sep treatment induced differential gene expression after culture in HRGECs cultured with LN flare serum. Addition of L-Sep induced genes involved in promoting endothelial function and enriched for pathways of NO biosynthetic and metabolic processes, fatty acid and lipid biosynthesis, neurotransmitter biosynthesis, reactive oxygen biosynthesis, vascular endothelial growth factor production, and regulation of smooth muscle contraction. Conclusions These results indicate that glomerular endothelial cells can mount an active inflammatory response in an LN serum environment. More importantly, L-Sep modulates gene expression in a fashion consistent with reduction of oxidative stress and increased NO production. These findings provide the rationale to target endothelial dysfunction to modulate LN with L-Sep as a therapeutic.
Published in
Lupus nephritis serum induces changes in gene expression in human glomerular endothelial cells, which is modulated by L-sepiapterin: implications for redox-mediated endothelial dysfunction
Russell DA, Van Beusecum JP, Markiewicz M et al. · Lupus science & medicine 2025 · PMID 40480647 · doi:10.1136/lupus-2025-001568
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE296560_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1259974 and SRA study SRP583711. Searching any of these in the dataset finder brings you back here.

Study design
5 × Healthy Control vs 5 × LN flare vs 5 × LN flare + LSep vs 4 × LN remission

Supports a between-group comparison across 19 samples.

How we read this: 4 replicated groups read from 19 sample titles; they account for 19 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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