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

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 IFN?, and behaving like normal primary cultures after 7 days in restrictive conditions, 37°C without IFN?), stimulated with TGFß 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 TGFß-stimulated TECs, while co-treating with S-adenosyl methionine (SAM) attenuated this dysfunctional phenotype. Overall design: 18 samples, 3 replicates, 6 conditions. Control, TGFß 10 ng/mL, nicotinamide (NAM) 1mM, TGFß + NAM, S-adenosyl methionine (SAM) 0.5mM, TGFß + SAM. Cells treated for 48h.