Acteoside ameliorates hepatic ischemia-reperfusion injury <i>via</i> reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks
Kexin Jia, Yinhao Zhang, Ranyi Luo, Runping Liu, Yajing Li, Jianzhi Wu, Kaihong Xie, Jia Liu, Shuo Li, Fei Zhou, Xiaojiaoyang Li
Abstract
, leading to the chemotaxis of neutrophils and accelerating immune damage in a vicious circle. Notably, ACT or HMGB1 siRNA effectively disrupted HMGB1-TLR3/4 interaction, leading to IRF1 inhibition and repairing LSEC functions, which was largely reversed by HMGB1 stimulation and IRF1-overexpressed liposomes with LSECs-targeted hyaluronic acid-derivative conjugated in mice. Collectively, ACT reversed the senescent fate of LSECs and restored sinusoidal networks by targeting HMGB1-TLR3/4-IRF1 signaling, thus providing protection against HIRI and offering the potential for new therapeutics development.
Topics & Concepts
HMGB1Cell biologyTLR3IRF1Reperfusion injuryBiologyCancer researchDampTLR4InflammationIschemiaPharmacologyImmunologyImmune systemSignal transductionInnate immune systemMedicineTranscription factorToll-like receptorInternal medicineBiochemistryMeteorologyPhysicsGeneImmune Response and InflammationImmune cells in cancerCancer, Hypoxia, and Metabolism