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NNMT overexpression promotes tubular senescence and fibrosis in human chronic kidney disease (NAM and SAM supplementation in TEC cells) [Series_2]

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. Co-treating the cells with nicotinamide (NAM) did not prevent the senescence and epithelial-to-mesenchymal transition in TGFβ-stimulated TECs, while co-treating with S-adenosyl methionine (SAM) attenuated this dysfunctional phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE280551 | GEO | 2025/11/20

REPOSITORIES: GEO

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NNMT overexpression promotes tubular senescence and fibrosis in human chronic kidney disease (NNMT inhibition in TEC cells) [Series_1]

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), stimulated with TGFβ to mimic the senescent and pro-fibrotic phenotypic shift of TECs during kidney disease. Co-treating the cells with the selective and membrane-permeable small molecule 5-amino-1-methylquinolinium iodide (NNMTi) significantly protected against senescence and epithelial-to-mesenchymal transition in TGFβ-stimulated TECs.

2025-11-20 | GSE280542 | GEO

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

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), 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.

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2025-04-10 | GSE286352 | GEO

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2025-11-20 | GSE248436 | GEO

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2023-03-11 | PXD029723 | Pride

Gene expression analysis of effects of Met on BMDMs co-cultured with COM-TECs.

Project description:Microarray analysis was used to assess the expression levels of mRNAs in bone marrow-derived macrophages (BMDMs) pretreated with metformin (Met) or PBS and co-cultured with renal tubular epithelial cells (TECs) or COM-TECs (NC vs. COM, COM vs. COM + Met).BMDMs and TECs were isolated from wild-type (WT) C57BL/6J mice. To developed a BMDM-COM-stimulated TECs co-culture system, BMDMs were plated in the upper chamber of 6-well Transwell plates with a pore size of 0.4 μm (Corning, USA), while TECs were plated in the lower chamber. In the COM and COM + Met groups, TECs were treated with COM (100 μg/mL) for 24 h and BMDMs were treated with Met (5.0mM) for 24 h.

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