ArticleJournal of diabetes investigation2025
The PKM2 activator TEPP-46 suppresses cellular senescence in hydrogen peroxide-induced proximal tubular cells and kidney fibrosis in CD-1
Article in Journal of diabetes investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- The biology of PKM2 in the metabolism and senescence in diabetic kidney disease.Journal of diabetes investigation · 2026Review
- circRNA_Atp8a1 Promotes Glycolytic Reprogramming in Damage of Intestinal Mucosal Barrier by Upregulating IGF2 through miR-200b-3p.Tissue engineering and regenerative medicine · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
AIM/
introductionSenescence is a key driver of age-related kidney dysfunction, including diabetic kidney disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and is associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to cellular senescence have not been elucidated. We hypothesized that PKM2 activation by TEPP-46 could suppress oxidative stress-induced renal tubular cell injury and cellular senescence. MATERIALS AND
methodsTo investigate the effects of PKM2 activation on oxidative stress-induced cellular senescence, we conducted β-galactosidase staining and western blot analysis on human primary renal tubular cells (pRPTECs) treated with hydrogen peroxide with or without TEPP-46. IL-6 levels and glycolytic flux were measured. Cell viability and apoptosis were assessed via the MTS assay and caspase 3 cleavage. For in vivo experiments, we utilized CD-1
resultsIn pRPTECs, hydrogen peroxide increased the number of β-galactosidase-positive cells, the expression of senescence markers (p16, p21, p53), and p38 phosphorylation; co-incubation with TEPP-46 suppressed these alterations. Hydrogen peroxide reduced cell viability, induced apoptosis, mesenchymal alterations, and increased lactate production and IL-6 secretion; co-incubation with TEPP-46 or a p38 inhibitor mitigated these effects. In CD-1
conclusionsPKM2 activation could be a molecular target for protection against senescence-associated organ damage, including diabetic kidney disease.
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