GEO series

Targeting Immunoproteasome in Macrophages Suppresses M1 Polarization and Ameliorates Experimental Emphysema via Activating NRF1 and NRF2-P62 Axis

GSE266962 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/05/31 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 24 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: Mus musculus (mouse)
Samples: 24 samples: 6 conditions, mostly with about 4 replicates eachGroups 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.

Summary (written by the submitters)

Chronic obstructive pulmonary disease (COPD) stands as the prevailing chronic airway ailment, characterized by chronic bronchitis and emphysema. Current medications fall short in treatment of these diseases, underscoring the urgent need for effective therapy. Prior research indicated immunoproteasome inhibition can alleviate various inflammatory diseases by modulating immune cell functions.

Read the full summary ↓

However, its therapeutic potential in COPD remains largely unexplored. Here, we observed elevated expression of immunoproteasome subunits LMP2 and LMP7 in bronchoalveolar lavage (BAL) macrophages collected from mouse with LPS/elastase-induced emphysema and M1 polarized macrophages in vitro. Subsequently, intranasal administration of the immunoproteasome-specific inhibitor ONX-0914 significantly mitigated emphysema-associated airway inflammation and improved lung function in mice, by suppressing M1 macrophage polarization. Mechanistically, ONX-0914 activated autophagy, and endoplasmic reticulum (ER) stress was not necessary for ONX- 0914-induced M1 suppression. Intriguingly, ONX-0914 upregulated the autophagy receptor p62/SQSTM1, which proved vital for the inhibitory effect of ONX-0914 on M1 polarization. Additionally, our research identified that the nuclear factor erythroid 2-related factor-2 (NRF2), but not NRF1, was responsible for the induction of p62. Finally, silencing both NRF1 and NRF2 partially counteracted ONX-0914-mediated M1 polarization inhibition. In summary, our findings suggest that targeting the immunoproteasome in macrophages holds promise as a therapeutic strategy for emphysema.

This dataset

Open GSE266962 in finder → Find more mouse RNA-seq datasets →

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.

Series matrix ↓

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 GSE266962_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

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.

Raw reads on ENA ↗

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 PRJNA1108805. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly with about 4 replicates each

PM, RNA-Seq, ×4 PM, ONX-0914, RNA-Seq, ×4 PM, LPS+IFN-γ, RNA-Seq, ×4 PM, LPS+IFN-γ+ONX-0914, RNA-Seq, ×4 PM, IL4, RNA-Seq, ×4 PM, IL4++ONX-0914, RNA-Seq, ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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

GSM8257455 PM, RNA-Seq, replicate1 PM, RNA-Seq,
GSM8257456 PM, RNA-Seq, replicate2 PM, RNA-Seq,
GSM8257457 PM, RNA-Seq, replicate3 PM, RNA-Seq,
GSM8257458 PM, RNA-Seq, replicate4 PM, RNA-Seq,
GSM8257459 PM, ONX-0914, RNA-Seq, replicate1 PM, ONX-0914, RNA-Seq,
GSM8257460 PM, ONX-0914, RNA-Seq, replicate2 PM, ONX-0914, RNA-Seq,
GSM8257461 PM, ONX-0914, RNA-Seq, replicate3 PM, ONX-0914, RNA-Seq,
GSM8257462 PM, ONX-0914, RNA-Seq, replicate4 PM, ONX-0914, RNA-Seq,
GSM8257463 PM, LPS+IFN-γ, RNA-Seq, replicate1 PM, LPS+IFN-γ, RNA-Seq,
GSM8257464 PM, LPS+IFN-γ, RNA-Seq, replicate2 PM, LPS+IFN-γ, RNA-Seq,
GSM8257465 PM, LPS+IFN-γ, RNA-Seq, replicate3 PM, LPS+IFN-γ, RNA-Seq,
GSM8257466 PM, LPS+IFN-γ, RNA-Seq, replicate4 PM, LPS+IFN-γ, RNA-Seq,
GSM8257467 PM, LPS+IFN-γ+ONX-0914, RNA-Seq, replicate1 PM, LPS+IFN-γ+ONX-0914,…
GSM8257468 PM, LPS+IFN-γ+ONX-0914, RNA-Seq, replicate2 PM, LPS+IFN-γ+ONX-0914,…
GSM8257469 PM, LPS+IFN-γ+ONX-0914, RNA-Seq, replicate3 PM, LPS+IFN-γ+ONX-0914,…
GSM8257470 PM, LPS+IFN-γ+ONX-0914, RNA-Seq, replicate4 PM, LPS+IFN-γ+ONX-0914,…
GSM8257471 PM, IL4, RNA-Seq, replicate1 PM, IL4, RNA-Seq,
GSM8257472 PM, IL4, RNA-Seq, replicate2 PM, IL4, RNA-Seq,
GSM8257473 PM, IL4, RNA-Seq, replicate3 PM, IL4, RNA-Seq,
GSM8257474 PM, IL4, RNA-Seq, replicate4 PM, IL4, RNA-Seq,
GSM8257475 PM, IL4++ONX-0914, RNA-Seq, replicate1 PM, IL4++ONX-0914, RNA-…
GSM8257476 PM, IL4++ONX-0914, RNA-Seq, replicate2 PM, IL4++ONX-0914, RNA-…
GSM8257477 PM, IL4++ONX-0914, RNA-Seq, replicate3 PM, IL4++ONX-0914, RNA-…
GSM8257478 PM, IL4++ONX-0914, RNA-Seq, replicate4 PM, IL4++ONX-0914, RNA-…

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