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Targeting Notch1-YAP Circuit Reprograms Macrophage Polarization and Alleviates Acute Liver Injury in Mice by Yan Yang; Ming Ni; Ruobin Zong; Mengxue Yu; Yishuang Sun; Jiahui Li; Pu Chen; Changyong Li is a Medicine article available to read on EtoBox.

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## Background & Aims Hepatic immune system disorder plays a critical role in the pathogenesis of acute liver injury. The intrinsic signaling mechanisms responsible for dampening excessive activation of liver macrophages are not completely understood. The Notch and Hippo-YAP signaling pathways have been implicated in immune homeostasis. In this study, we investigated the interactive cell signaling networks of Notch1/YAP pathway during acute liver injury. ## Methods Myeloid-specific Notch1 knockout (Notch1^M-KO^) mice and the floxed Notch1 (Notch1^FL/FL^) mice were subjected to lipopolysaccharide/D-galactosamine toxicity. Some mice were injected via the tail vein with bone marrow–derived macrophages transfected with lentivirus-expressing YAP. Some mice were injected with YAP siRNA using an in vivo mannose-mediated delivery system. ## Results We found that the activated Notch1 and YAP signaling in liver macrophages were closely related to lipopolysaccharide/D-galactosamine-induced acute liver injury. Macrophage/neutrophil infiltration, proinflammatory mediators, and hepatocellular apoptosis were markedly ameliorated in Notch1^M-KO^ mice. Importantly, myeloid Notch1 deficiency depresse

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Author

Yan Yang; Ming Ni; Ruobin Zong; Mengxue Yu; Yishuang Sun; Jiahui Li; Pu Chen; Changyong Li

Publisher

Elsevier

Published

2023

Language

EN

Field

Medicine (Health Sciences)