P16-positive senescent cells promote DKD by the dysregulation of glycolysis and mitochondrial metabolism.

ABSTRACT: Diabetic kidney disease (DKD) is characterized by kidney damage and abnormal renal energy metabolism, but the molecular mechanism of DKD is still unclear. In this study, we show that p16- positive senescent cells are an important regulator in the progression of DKD. The expression of p16 and senescence are increased in the kidneys of DM mice and DKD patients. To better understand the role of p16 in DKD, we induce type 1 diabetes in INK-ATTAC mice, a mouse model that allows the selective ablation of p16-expressing cells upon administration of the drug AP20187. We found that clearance of p16-positive cells, most of them are senescent cells, (1) decreased senescence and the expression of the components of the senescence-associated secretory phenotypes (SASPs), (2) restored kidney adenosine tr

SUBMITTER: Lu X 

PROVIDER: S-EPMC12311014 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature