Chk2 Modulates Bmi1-Deficiency-Induced Renal Aging and Fibrosis via Oxidative Stress, DNA Damage, and p53/TGFβ1-Induced Epithelial-Mesenchymal Transition
Jinhong Lü, Weiwei Sun, Boyang Liu, Jinge Zhang, Rong Wang, David Goltzman, Dengshun Miao
Abstract
) increased TGFβ1 expression, and EMT in RTECs and was partly reversed by p53 inhibition. Together, Bmi1 deficiency causes oxidative stress and DDR-mediated RTEC senescence/SASP, thus activating p53 and TGFβ1 to induce EMT and age-related fibrosis. However, blocking DDR (via Chk2 knockout) or p53 ameliorates these changes. Our study reveals mechanisms whereby Bmi1 preserves renal structure and function during aging by suppressing DDR and p53/TGFβ1-mediated EMT. These pathways represent potential targets for detecting and attenuating age-related renal decline.
Topics & Concepts
Oxidative stressDNA damageOxidative damageEpithelial–mesenchymal transitionTransforming growth factorFibrosisCancer researchMesenchymal stem cellDNAChemistryCell biologyTransition (genetics)MedicineBiologyBiochemistryPathologyGeneTrace Elements in HealthRenal and related cancersPluripotent Stem Cells Research