Extracellular vesicle-mediated bidirectional communication between the liver and other organs: mechanistic exploration and prospects for clinical applications

Mo, Wenhui; Peng, Yunke; Zheng, Yanyi; Zhao, Shenglan; Deng, Liling; Fan, Xiaoli

doi:10.1186/s12951-025-03259-4

Table 2 EV-mediated communication between the liver and other organs

From: Extracellular vesicle-mediated bidirectional communication between the liver and other organs: mechanistic exploration and prospects for clinical applications

EV cargo	Source	Target	(Disease) Model	Effect or Mechanism	Reference
Group 1
HSP70	Bone	Liver	Liver ischemia-reperfusion	Treat liver damage by controlling the ratio of Th17 cells to Tregs through the PI3K/mTOR axis	[70]
Unknown	Bone	Liver	Periodontitis	Enhance SCD-1 expression and suppress AMPK signaling pathway, exacerbating fatty liver	[71]
LRG1	Liver	Bone	SIRT2 deficiency	Reduce NF-κB p65 nuclear translocation and inhibit osteoclast differentiation, which reduce bone loss	[67]
Fasn	Liver	Bone	Type 2 diabetes	Increase ectopic fatty acid synthesis in PDLCs, activate NLRP3 inflammasome, and induce GSDMD cleavage, which lead to PDLCs pyroptosis and thus exacerbate bone loss	[68]
Unknown	Liver	Bone	Mandibular defect	Increase osteogenesis-related gene expression in mandibular mesenchymal stem cells, which promote mandibular healing	[69]
Group 2
miR-1	Liver	Cardiovascular system	ApoE^−/− mice, HFD	Promote atherosclerosis by inhibiting KLF4 and activating NF-κB	[11]
miR-30a-3p	Liver	Cardiovascular system	High-fat, high-cholesterol diet-fed ApoE^−/− mice	Promote foam cell formation and atherosclerosis by inhibiting ABCA1-mediated cholesterol efflux	[12]
novel-miR-7	Liver	Cardiovascular system	NAFLD	Increase endothelial permeability by targeting the LAMP1/Cathepsin B/NLRP3 inflammasome axis	[74]
miR-122-5p	Liver	Cardiovascular system	Exercise	Enhance endothelial fatty acid oxidation by downregulating AGPAT1, which promote angiogenesis and wound healing	[78]
miR-122	Liver	Cardiovascular system	Obesity	Promote obesity-related cardiomyopathy progression by inhibiting Arl-2 to impair mitochondrial function	[76]
Group 3
Unknown	Gut	Liver	HFD/CCl4-induced liver injury	Inhibit HSCs activation and reduce fibrosis marker gene expression	[6]
Unknown	Gut	Liver	NASH	Exacerbate liver damage by activateing HSCs, which involved in fibrosis progression, and impairing hepatocyte integrity	[84]
Unknown	Gut	Liver	HFD/CCL4-induced liver injury	Inhibit TLR expression and upregulate PPAR to exert anti-inflammatory effects	[7]
Microbial DNA	Gut	Liver	HFD	Activate cGAS/STING pathway to enhance inflammation and impair insulin sensitivity	[83]
Unknown	Gut	Liver	Diet-induced obesity	May promote liver inflammation via TLR4-mediated signaling	[85]
Unknown	Gut	Liver	Gut ischemia-reperfusion	Cause liver damage by polarizing Kupffer cells toward M1 and increasing pro-inflammatory cytokine mRNA expression	[82]
HMGB1	Gut	Liver	HFD	Trigger hepatic steatosis	[87]
Group 4
miR-29s	Pancreas	Liver	HFD	Reduce AKT phosphorylation induced by insulin, leading to systemic insulin resistance	[89]
Unknown	Liver	Pancreas	Insulin resistance	Regulate glucose homeostasis by increasing insulin gene expression and AKT phosphorylation	[9]
miR-126a-3p	Liver	Pancreas	Diet-induced obesity	Possibly exacerbate diabetes by promoting β-cell apoptosis through inhibition of IRS2 expression	[90]
Group 5
TNF-α	Liver	Brain	Hyperammonemia	Induce motor incoordination by activating TNFR1-CCL2-BDNF-TrkB-KCC2 and TNFR1-NF-κB-glutaminase-GAT3 pathways	[93]
ApoE4	Liver	Brain	Age-related thyroid deficiency	Increase cholesterol in neurons, trigger ROS elevation, which activate NLRP3 inflammasome, leading to cognitive, motor, and emotional impairments	[94]
miR-143-3p	Pituitary	Liver	—	Promote hepatocyte proliferation by downregulating IGFBP5 to increase IGF-1 expression and activating Wnt/β-catenin pathway	[96]
Unknown	Brain	Liver	Traumatic brain injury	Elevate serum AST and ALT levels, cause histopathological changes in liver, and ultimately induce hepatocyte apoptosis	[95]
Group 6
miR-194	Liver	Lung	Hepatopulmonary syndrome(HPS)	Likely promote angiogenesis by targeting THBS1, STAT1, and LIF, which worsen HPS	[99]
miR-122-5p	Liver	Lung	Liver ischemia-reperfusion	Cause acute lung injury by inhibiting SOCS-1 expression and activating NF-κB to promote inflammation and M1 macrophage polarization	[101]
Unknown	Liver	Lung	Acute pancreatitis	Increase expression of pro-inflammatory factors to promote lung inflammation	[102]
Group 7
miR-687	Kidney	Liver	Kidney ischemia-reperfusion	Promote liver inflammation and apoptosis, which cause liver injury	[10]
Group 8
miR-378a-3p	Adipose	Liver	Cold exposure	Promote gluconeogenesis by targeting p110α and downregulating AKT phosphorylation	[106]
miR-141-3p	Adipose	Liver	Obesity	Increase AKT phosphorylation levels by downregulating PTEN, leading to increased insulin sensitivity	[108]
Unknown	Adipose	Liver	Obesity with NAFLD	Downregulate AKT phosphorylation, which causes insulin resistance	[109]
miR-155	Adipose	Liver	Obesity	Inhibit PPARγ to reduce insulin-induced AKT phosphorylation, leading to insulin resistance	[111]
CD36	Adipose	Liver	HFD	Induction of lipid accumulation and inflammation leading to exacerbation of NAFLD	[112]
miR-122	Adipose	Liver	NAFLD	Enhance glucose and lipid metabolism by inhibiting Sirt1 expression, which worsen liver injury	[114]
miR-132-3p	Adipose	Liver	Cold exposure	Suppresse hepatic Srebf1 expression in order to reduce hepatic lipogenesis for cold adaptation	[107]
miR-103	Adipose	Liver	NASH	Interact with PTEN to inhibit hepatocyte autophagy so that involve in NASH progression	[115]
miR-130a-3p	Liver	Adipose	High-fat diet-fed miR-130a knockout or overexpression mice	Improve glucose intolerance by inhibiting PHLPP2 to activate AKT-AS160-GLUT4 pathway	[8]
miRNAs	Liver	Adipose	HFD	Increase lipid production to remodel adipose tissue	[120]
miR-3075	Liver	Adipose	Early-onset obesity	Downregulation of FA2H expression results in higher levels of insulin-stimulated AKT phosphorylation, which in turn increases glucose uptake to exert a compensatory effect	[118]
TM4SF5	Liver	Adipose	TM4SF5 knockout or overexpression	Improve glucose tolerance and maintain glucose homeostasis	[119]
Unknown	Liver	Adipose	High-energy diet	Aggravate adipocyte inflammation and lipid accumulation	[121]

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