Downregulation of Akt induces proximal tubule epithelial cell apoptosis via FOXO and BIM pathway in proteinuric States.

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 an

SUBMITTER: Chhaing R 

PROVIDER: S-EPMC12568932 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature