Drug Design, Development and Therapy (Dec 2024)
CXCR2 Activated JAK3/STAT3 Signaling Pathway Exacerbating Hepatotoxicity Associated with Tacrolimus
Abstract
Xiao Chen,1,* Ke Hu,2,* Yue Zhang,2 Su-Mei He,3 Dong-Dong Wang2 1School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, 215153, People’s Republic of China*These authors contributed equally to this workCorrespondence: Su-Mei He, Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, 215153, People’s Republic of China, Email [email protected] Dong-Dong Wang, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China, Email [email protected]: Tacrolimus could induce hepatotoxicity during clinical use, and the mechanism was still unclear, which posed new challenge for the prevention and treatment of tacrolimus-induced hepatotoxicity. The aim of this study was to investigate the mechanism of tacrolimus-induced hepatotoxicity and provide reference for drug development target.Methods: In this study, biochemical analysis, pathological staining, immunofluorescent staining, immunohistochemical staining, transcriptomic analysis, Western blotting was used to investigate the mechanism of tacrolimus-induced hepatotoxicity in gene knockout mice and Wistar rats.Results: In gene knockout mice, compared to wild-type mice, CXCR2-deficiency alleviated tacrolimus-induced hepatotoxicity (P
