Inhibition of MCL-1 to eliminate senescent cells and mitigate renal fibrosis in aristolochic acid nephropathy.

ABSTRACT: The role of tubular epithelial cells (TEC) senescence in the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remains debated due to the complexity of senescent cell populations and their pro-survival mechanisms. To directly assess the contribution of TEC senescence to AKI-to-CKD progression, we employed an aristolochic acid nephropathy (AAN) mouse model. Here, we demonstrated that AAI-induced DNA damage specifically drives TEC senescence during AKI-to-CKD progression. Concomitant with the emergence of senescence, immunofluorescence staining revealed the expression of anti-apoptotic proteins, including BCL-2, BCL-xL, and MCL-1, within KIM1⁺ tubules-a marker of tubular injury. To further characterize these senescent cells, we integrated this model with snRNA-Seq da

SUBMITTER: Gao P 

PROVIDER: S-EPMC12824375 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature