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Transglutaminase 2 regulates vimentin-dependent proteostasis during macrophage activation in sepsis

GSE301229 Mus musculus (mouse) RNA-seq (gene expression) 21 samples Submitted 2026/01/29 Platform GPL28457Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 21 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
21 samples: 7 conditions, mostly in duplicateGroups 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)
Sepsis-associated liver dysfunction (SALD) is a life-threatening condition with a high mortality rate and no mechanism-based therapy. In this study, we identified transglutaminase 2 (TG2) as a druggable driver of macrophage-mediated liver inflammation in murine lipopolysaccharide (LPS)-induced sepsis. Pharmacological inhibition of TG2 significantly improved survival and reduced multi-organ inflammation, with the liver as a primary therapeutic target.
Read the full summary ↓
Mechanistically, TG2 activity was upregulated in macrophages, where it cross-linked vimentin to promote oligomerization and intermediate filament remodeling. Genetic ablation of TG2 or vimentin suppressed macrophage cytokine production and attenuated LPS-induced inflammation. Notably, vimentin-deficient macrophages exhibited enhanced proteasome recruitment to detergent-insoluble protein aggregates, accelerating the degradation of proinflammatory mediators such as TRAF6, thereby dampening NF-κB signaling. Proteomic profiling revealed a previously unrecognized Rab27a-positive vesicle trafficking pathway for inflammatory aggregate clearance. Together, these findings define a TG2–vimentin axis that controls macrophage activation through proteostasis regulation, linking cytoskeletal remodeling to inflammatory signaling. Our study suggests that targeting this axis, either via TG2 inhibition or modulation of vimentin-dependent proteostasis, represents a novel therapeutic strategy for the treatment of SALD.
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 GSE301229_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 PRJNA1284302 and SRA study SRP597828. Searching any of these in the dataset finder brings you back here.

Study design
7 conditions, mostly in duplicate
WT RAW264.7 cells, PBS, 24 h, ×2 WT RAW264.7 cells, 1 µg/mL LPS, 24 h, ×2 WT RAW264.7 cells, 1 µg/mL LPS plus 0.5 mM CT… ×2 WT RAW264.7 cells, PBS, 12 h, ×2 WT RAW264.7 cells, 1 µg/mL LPS, 12 h, ×2 Vim-KO RAW264.7 cells, PBS, 12 h, ×2 Vim-KO RAW264.7 cells, 1 µg/mL LPS, 12 h, ×2 WT C57BL/6J, PBS i.p ×1 +6 more

Supports a between-group comparison across 14 samples.

How we read this: 7 replicated groups read from 21 sample titles; they account for 14 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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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.