Fig. 4

Overview of the communication network between the liver, brain, lungs, and kidneys mediated by EVs. (a) The liver-pancreas axis mainly reflects the effects of EVs on insulin function, which is essential for regulating energy metabolism. (b) The liver-brain/pituitary axis reveals that EVs carrying different substances shuttle between the liver and brain/pituitary, supporting motor and cognitive functions as well as liver health. (c) The liver-lung axis reveals the pathological effects of liver-derived EVs on the lungs, contributing to the understanding of lung disease progression. (d) The liver-kidney axis research focuses on the impact of kidney disease on hepatic function, and this axis of interaction has yet to be studied in depth. Overall, these axes reflect the impact of interactions between the liver and other organs on physiological or disease states. They are important in maintaining overall homeostasis. Abbreviation: AKT: protein kinase B; TNFR1: tumor necrosis factor receptor-1; CCL2: C-C motif chemokine 2; BDNF: brain-derived neurotrophic factor; TrkB: tropomyosin-related kinase B; KCC2: K-Cl cotransporter 2; GAT3: GABA transporter type 3; ApoE4: apolipoprotein E 4; sEVs: small extracellular vesicles; Wnt: wingless-related integration site; HPS: hepatopulmonary syndrome; PMVEC: pulmonary microvascular endothelial cell