Zhi Bo Zhao, Julian A Marschner, Takamasa Iwakura, Chenyu Li, Manga Motrapu, Meisi Kuang, Bastian Popper, Andreas Linkermann, Jan Klocke, Philipp Enghard, Yoshiharu Muto, Benjamin D Humphreys, Helena Erlandsson Harris, Paola Romagnani, Hans-Joachim Anders
SIGNIFICANCE STATEMENT: Cells undergoing necrosis release extracellular high mobility group box (HMGB)-1, which triggers sterile inflammation upon AKI in mice. Neither deletion of HMGB1 from tubular epithelial cells, nor HMGB1 antagonism with small molecules, affects initial ischemic tubular necrosis and immediate GFR loss upon unilateral ischemia/reperfusion injury (IRI). On the contrary, tubular cell-specific HMGB1 deficiency, and even late-onset pharmacological HMGB1 inhibition, increased functional and structural recovery from AKI, indicating that intracellular HMGB1 partially counters the effects of extracellular HMGB1...
March 1, 2023: Journal of the American Society of Nephrology: JASN