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NNMT overexpression promotes tubular senescence and fibrosis in human chronic kidney disease (NNMT inhibition and SAM supplementation in TEC cells)

ABSTRACT: Renal tubular epithelial cells (TECs) are increasingly recognized as the central locus of chronic kidney disease and renal fibrosis. Here, we used conditionally immortalized TECs (expressing SV40 large T antigen at permissive conditions, 33°C with IFNγ, and behaving like normal primary cultures after 7 days in restrictive conditions, 37°C without IFNγ), stimulated with TGFβ to mimic the senescent and pro-fibrotic phenotypic shift of TECs during kidney disease. TGFβ stimulation and co-treatment with either the small-molecule NNMT inhibitor 5-amino-1-methylquinolinium iodide (NNMTi) or S-adenosyl methionine (SAM) altered the DNA methylation profile of the cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE310712 | GEO | 2025/11/20

REPOSITORIES: GEO

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NNMT overexpression promotes tubular senescence and fibrosis in human chronic kidney disease (Nnmt overexpressing TEC cells) [Series_3]

Project description:Renal tubular epithelial cells (TECs) are increasingly recognized as the central locus of chronic kidney disease and renal fibrosis. Here, we used conditionally immortalized TECs (expressing SV40 large T antigen at permissive conditions, 33°C with IFNγ, and behaving like normal primary cultures after 7 days in restrictive conditions, 37°C without IFNγ) and genetically overexpressed Nnmt (Nnmt-OE) by means of lentiviral transduction of a mock or Nnmt expression construct. In the TGFβ model mimicking the senescent and pro-fibrotic changes in TECs, Nnmt overexpression resulted in an aggravated phenotype.

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| PRJNA472964 | ENA

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