ArticleScientific reports2025
Downregulation of Akt induces proximal tubule epithelial cell apoptosis via FOXO and BIM pathway in proteinuric States.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Molecular Mechanisms of Cadmium-Induced Apoptosis in Fish Cells: A Review.International journal of molecular sciences · 2026Review
- The Anti-Apoptotic Activity of β-Synuclein Mediated via Akt Signaling Is Severely Lost During Prion Infection.International journal of molecular sciences · 2026Article
- Tubulointerstitial inflammation and fibrosis induced by proteinuria: fresh insights.Frontiers in pharmacology · 2026Review
- Gene regulatory networks involved in activation of Notch signaling by AGEs in the pathogenesis of diabetic kidney disease.PloS one · 2026Article
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Abstract
Proteinuria is a widely utilized surrogate marker in clinical practice for its predictive and prognostic value. The mechanistic link between proteinuria and progression remains elusive. Proximal tubule epithelial cells(PTEC) retrieve albumin in the glomerular filtrate via receptor mediated endocytosis facilitated by megalin-cubilin complex. We reported that cell-survival protein, Akt, phosphorylates cargo binding endocytic adaptor protein to megalin, disabled-2(Dab2). We hypothesize that downregulation of Akt signaling as a result of overwhelmed endocytic machinery in albumin overload is linked to PTEC apoptosis in proteinuric states. We show that cell culture and animal model of albumin overload inhibited phosphorylation of Akt in association with apoptosis in PTEC. Chemical inhibition and overexpression of Akt by constitutively active Akt plasmid exacerbated and alleviated apoptosis respectively in response to albumin overload in PTEC. Mouse with targeted inhibition of Akt1 and Akt2 in PTEC (Akt1/2lox/loxSGLT2cre) displayed perturbed albumin endocytosis at baseline. Albumin overload in Akt1/2
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