Fatty acid-binding protein 4 is a therapeutic target for septic acute kidney injury by regulating inflammatory response and cell apoptosis

• DOI: 10.1038/s41419-022-04794-w
• Publication Date: 2022-04-11T19:07:52Z
• Authors: Bo Wang; Jun Xu; Qian Ren; Lu Cheng; Fan Guo; Yan Liang; Letian Yang; Zhouke Tan; Ping Fu; Liang Ma
• Keywords: Inflammation; Lipopolysaccharides; 0301 basic medicine; QH573-671; Apoptosis; Acute Kidney Injury; Fatty Acid-Binding Proteins; Article; 3. Good health; Toll-Like Receptor 4; Mice; 03 medical and health sciences; Sepsis; Animals; Cytology

Abstract Sepsis is a systemic inflammatory state in response to infection, and concomitant acute kidney injury (AKI) significantly increases morbidity mortality. Growing evidence suggests that fatty acid-binding protein 4 (FABP4) critically involved diseases, while its role septic AKI remains unknown. Here, FABP4 was mainly upregulated renal tubular epithelial cells (RTECs) following cecal ligation puncture (CLP)- or lipopolysaccharide (LPS)-induced AKI. inhibition by genetic deletion BMS309403 treatment both attenuated dysfunction pathological CLP- LPS-treated mice. Notably, RTEC-specific of also showed similar renoprotective effects. Moreover, alleviated inflammation apoptosis CLP-injured kidneys LPS-stimulated mouse cells. Mechanistically, TLR4 blockage improved sepsis-induced injury, as well suppressed c-Jun phosphorylation expression, where knockdown inhibited level. Meanwhile, reduced the elevated phosphorylated c-Jun, levels MyD88 were uninfluenced. Collectively, increased RTECs dependent on TLR4/c-Jun signaling activation contributes forming positive feedback loop with aggravate Thus, may be therapeutic target for