High glucose induced senescence in proximal tubular cells, whose SASP-conditioned medium then triggered epithelial-mesenchymal transition in distal tubular cells and fibroblast activation. EGCG, L-theanine, and theophylline suppressed these effects while restoring SIRT1/PGC-1alpha signaling.
Key findings
- High glucose increased senescence markers, p21, S-phase arrest, and SASPs while suppressing SIRT1/PGC-1alpha; measured p38, GSK-3beta, and beta-catenin were unchanged. SASPs reduced E-cadherin/ZO-1 and increased vimentin, fibronectin, collagen, and stress fibers, effects suppressed by all three compounds.
Why this matters globally
Linking tubular senescence to paracrine fibrosis helps explain disease progression and may reveal senomorphic targets. Glucose-lowering, antioxidant, and SIRT1-specific effects must be disentangled and confirmed in tissue.
Thai researcher contribution
Siriraj's Medical Proteomics Unit conducted the mechanistic program, combining renal-cell, proteomics, and fibrosis expertise with tea bioactives.
Limitations to consider
Cell-culture glucose and compound concentrations are not accompanied by doses, osmotic controls, pharmacokinetic relevance, or cytotoxicity in the abstract. Abolished refers to markers under selected conditions, not disease elimination. No animal, patient, or renal-function outcomes were studied.