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Targeting Set7 in an experimental model of diabetic nephropathy

GSE158626 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 28 samples Submitted 2024/04/17 Platform GPL24676Platform GPL21103
Summary
Set7 knockout (Set7KO) improved glomerular structure and albuminuria in a mouse model of diabetes. Analysis of mouse single-cell RNA-sequencing data showed dynamic transcriptional changes in diabetic renal cells. Set7KO controls phenotype switching of GEN cell populations through transcriptional regulation of the insulin growth factor binding protein 5 (IGFBP5). Chromatin immunoprecipitation assays confirmed that the expression of the IGFBP5 gene was associated with mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). This generalizability was investigated in human renal and circulating hyperglycemic cells exposed to TGFb1. We showed that the highly selective Set7 inhibitor PFI-2 attenuated indices associated with renal cell damage and mesenchymal transition, specifically (1) reactive oxygen species production, (2) IGFBP5 gene regulation, and (3) expression of mesenchymal markers. Furthermore, renal benefit observed in Set7KO diabetic mice closely corresponds in human glomerular endothelial cells with PFI-2 inhibition or Set7 shRNA silencing.
Published in
Set7 Methyltransferase and Phenotypic Switch in Diabetic Glomerular Endothelial Cells
Maxwell S, Okabe J, Kaipananickal H et al. · Journal of the American Society of Nephrology : JASN 2024 · PMID 38630537 · doi:10.1681/ASN.0000000000000345
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Direct links to NCBI, no account and no request form: the whole study as GSE158626_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA666001 and SRA study SRP285544. Searching any of these in the dataset finder brings you back here.

Study design
9 conditions, mostly with about 4 replicates each
GEC_NG ×4 GEC_PFI ×4 GEC_TGF ×4 KD_TGF ×4 NT_TGF ×4 Setd7 KO Kidney - Control ×2 Setd7 KO Kidney - Diabetic ×2 Setd7 WT Kidney - Control ×2 +1 more

Supports a between-group comparison across 28 samples.

9 replicated groups read from 28 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.

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