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Soluble αKlotho interacts with Hsp90aa1 to inhibit the chaperone machinery-mediated Hif1α stabilization and alleviate CKD-induced vascular calcification

GSE280375 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/10/26 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 3 × MA-VSMCs, Control, vs 3 × MA-VSMCs, calcium medium, vs 3 × MA-VSMCs, calcium medium, LV-Klotho, vs 3 × MA-VSMCs, calcium medium, LV-Vector,Groups 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)
Vascular calcification is the major risk factor for increased cardiovascular morbidity and mortality in patients with CKD, especially those with advanced renal diseases. However, once mineral deposits form in vascular tissue, no specific therapies can completely arrest or reverse the progression of calcification. Here, we identified that decreased serum soluble αKlotho levels are characteristic events in the development of vascular calcification in patients with early CKD.
Read the full summary ↓
We employed a transcriptomicsapproach, as well as in vitro and in vivo vascular calcification models, and determined that soluble αKlotho specifically suppressed Hsp90aa1 activation-mediated osteogenic transdifferentiation of VSMCs and vascular calcification. Moreover, we revealed that the phosphorylation of Hsp90aa1 at Thr5/7 modulated its chaperone activity to stabilize Hif1α, thereby playing a causative role in the pathogenesis of vascular calcification in response to CKD. Upregulation of soluble αKlotho expression in VSMCs enhanced the interaction with Hsp90aa1, which abolished Hsp90aa1-Hif1α axis activation in response to osteogenic induction. Together, these results identify a key pathway in VSMCs that mediates vascular calcification, which could be used as a potential therapeutic target.
This dataset
Open GSE280375 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 GSE280375_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 PRJNA1178121 and SRA study SRP541000. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × MA-VSMCs, Control, vs 3 × MA-VSMCs, calcium medium, vs 3 × MA-VSMCs, calcium medium, LV-Klotho, vs 3 × MA-VSMCs, calcium medium, LV-Vector,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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