Research Paper Volume 14, Issue 20 pp 8179—8204

Crosstalk between age accumulated DNA-damage and the SIRT1-AKT-GSK3ß axis in urine derived renal progenitor cells


Figure 6. Gene regulatory network associated with the aging process in UdRPCs. SIRT1 protein is in the cell nucleus (purple circle) and can be induced by resveratrol as well as the renal progenitor-regulating transcription factor-SIX2. SIRT1 protein is positively correlated with mRNA expression of the renal stem cell markers CD133 and SIX2 and has major implications in the self-renewal of UdRPCs. SIRT1 is involved in deacetylation and thereby activation of protein kinase B (AKT) as well as deacetylation and thereby inactivation of ß-Catenin. AKT can be activated through phosphorylation by ATM. Activated AKT dephosphorylates and thereby inactivates GSK3β. GSK3β phosphorylates ß-Catenin, which then gets disassembled by the proteasome. Unphosphorylated and acetylated ß-Catenin is transferred to the nucleus, where it binds to TCF4 and induces nephrogenesis via activated WNT signaling.