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

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 the selective and membrane-permeable small molecule 5-amino-1-methylquinolinium iodide (NNMTi) significantly protected against senescence and epithelial-to-mesenchymal transition in TGFß-stimulated TECs. Overall design: 12 samples, 3 replicates, 4 conditions. Control, TGFß 10 ng/mL, NNMTi (5-amino-1-methylquinolinium) 50 µM, TGFß + NNMTi. Cells treated for 48h.