TIMP2 protects against sepsis-associated acute kidney injury by cAMP/NLRP3 axis-mediated pyroptosis
Dongxue Xu, Jun Jiang, Ye Liu, Jingjing Pang, Jinmeng Suo, Yiming Li, Zhiyong Peng
Abstract
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.
Topics & Concepts
PyroptosisMedicineAcute kidney injurySepsisPharmacologyInternal medicineInflammasomeInflammationInflammasome and immune disordersHeme Oxygenase-1 and Carbon MonoxideGout, Hyperuricemia, Uric Acid