TIMP2 promotes AKI-CKD transition by inducing tubular maladaptive repair and cell senescence via targeting Wnt/β-catenin signalling.

ABSTRACT:

Background

Acute kidney injury (AKI) frequently progresses to chronic kidney disease (CKD), but the underlying mechanisms of this transition remain unclear. While TIMP2 is a known biomarker for AKI, its direct pathogenic role in the AKI-CKD transition has not been fully elucidated.

Methods

TIMP2 expression was evaluated in multiple murine models, including unilateral ischemia-reperfusion injury (UIR), unilateral ureteral obstruction (UUO), and cisplatin-induced nephropathy. To investigate its function, we employed a tubule-specific, inducible TIMP2 knockout mouse model (Ksp-CreERT2; TIMP2fl/fl) and a tubular overexpression model.

Results

TIMP2 was significantly upregulated during the AKI-CKD transition across all tested models. Tubule-specific deletion of TIMP2 marked

SUBMITTER: Xu D 

PROVIDER: S-EPMC12852052 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature