TIMP2 protects against sepsis-associated acute kidney injury by cAMP/NLRP3 axis-mediated pyroptosis

作者：Dongxue Xu, Jun Jiang, Ye Liu, Jingjing Pang, Jinmeng Suo, Yiming Li, Zhiyong Peng · 发表于：American Journal of Physiology-Cell Physiology · 年份：2024 · DOI：10.1152/ajpcell.00577.2023 · 被引用次数：19 · 研究领域：Inflammasome and immune disorders、Heme Oxygenase-1 and Carbon Monoxide、Gout, Hyperuricemia, Uric Acid

Tissue inhibitor of metalloproteinase 2 (TIMP-2) has been found to be the best biomarker for predicting the risk of sepsis-associated acute kidney injury (SA-AKI). However, its role and the underlying mechanism in SA-AKI remain elusive. The authors demonstrated in this study using kidney tubule-specific knockout mice model of SA-AKI and primary renal tubule cells stimulated with lipopolysaccharide (LPS) that extracellular TIMP-2 promoted NOD-like receptor protein 3 (NLRP3) ubiquitination and autophagy-dependent degradation by increasing intracellular cyclic adenosine monophosphate (cAMP), thus attenuated pyroptosis and alleviated renal damage.