# Extracellular Vesicles in Liver Fibrosis: Pathogenic Messengers, Diagnostic Biomarkers, and Therapeutic Nanovectors

**Authors:** Xinyi Zhao, Junyan Zhu, Tianyi Zhang, Wenrong Xu, Hui Qian

PMC · DOI: 10.3390/pharmaceutics18020230 · Pharmaceutics · 2026-02-11

## TL;DR

This review explores how extracellular vesicles contribute to liver fibrosis and their potential as diagnostic tools and treatment options.

## Contribution

The paper provides new insights into the role of extracellular vesicles in liver fibrosis and their therapeutic potential.

## Key findings

- Extracellular vesicles mediate intercellular communication and contribute to liver fibrosis progression.
- EVs can serve as biomarkers for diagnosing and predicting the prognosis of liver fibrosis.
- EVs show potential as therapeutic nanovectors for treating liver fibrosis.

## Abstract

Liver fibrosis (LF) is the final common pathological outcome of various chronic liver diseases. Advanced LF can progress to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Currently, liver transplantation remains the main clinical treatment for advanced LF, but its application is limited by donor availability and unavoidable complications. Extracellular vesicles (EVs), nanoscale particles actively released by hepatic cells, including hepatocytes, hepatic stellate cells (HSCs), and macrophages), circulate in bodily fluids carrying cell-specific cargoes (e.g., RNAs, proteins). EVs mediate intercellular communication via their specific cargo profiles and contribute to the progression in LF. Increasing evidence indicates that tracking changes in the quantity and composition of EVs in LF can aid in disease diagnosis and prognosis prediction. This review discusses the pathological role of EVs in LF development and their potential as biomarkers and therapeutic targets, and provides new perspectives for future research and treatment advances.

## Linked entities

- **Diseases:** cirrhosis (MONDO:0005155), liver failure (MONDO:0100192), hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, MIR27B (microRNA 27b) [NCBI Gene 407019] {aka MIR-27b, MIRN27B, miRNA27B}, BMP7 (bone morphogenetic protein 7) [NCBI Gene 655] {aka OP-1}, SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678] {aka BM-40, OI17, ON, ONT}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, MIR192 (microRNA 192) [NCBI Gene 406967] {aka MIRN192, miR-192, miRNA192}, MIR19B1 (microRNA 19b-1) [NCBI Gene 406980] {aka C13orf25, MIR19B, MIRH1, MIRHG1, MIRN19B1, miR-19b-1}, Slc7a11 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 11) [NCBI Gene 26570] {aka 9930009M05Rik, sut, xCT}, LIMA1 (LIM domain and actin binding 1) [NCBI Gene 51474] {aka EPLIN, LDLCQ8, SREBP3}, SLIT3 (slit guidance ligand 3) [NCBI Gene 6586] {aka MEGF5, SLIL2, SLIT1, Slit-3, slit2}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, H2AJ (H2A.J histone) [NCBI Gene 55766] {aka H2AFJ}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, NR0B2 (nuclear receptor subfamily 0 group B member 2) [NCBI Gene 8431] {aka SHP, SHP1}, CCNE1 (cyclin E1) [NCBI Gene 898] {aka CCNE, pCCNE1}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, TNFRSF10B (TNF receptor superfamily member 10b) [NCBI Gene 8795] {aka CD262, DR5, KILLER, KILLER/DR5, TRAIL-R2, TRAILR2}, SPHK1 (sphingosine kinase 1) [NCBI Gene 8877] {aka SPHK}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, LOXL2 (lysyl oxidase like 2) [NCBI Gene 4017] {aka LOR, LOR2, WS9-14}, SOCS1 (suppressor of cytokine signaling 1) [NCBI Gene 8651] {aka AISIMD, CIS1, CISH1, JAB, SOCS-1, SSI-1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, MIR1225 (microRNA 1225) [NCBI Gene 100188847] {aka MIRN1225}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, Mir26a-1 (microRNA 26a-1) [NCBI Gene 387218] {aka Mirn26a, Mirn26a-1, miR-26a, mir-26a-1}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, Ccl4 (C-C motif chemokine ligand 4) [NCBI Gene 20303] {aka AT744.1, Act-2, MIP-1B, Mip1b, Scya4}, Lamp2 (lysosomal-associated membrane protein 2) [NCBI Gene 16784] {aka CD107b, LGP-B, Lamp II, Lamp-2, Lamp-2a, Lamp-2b}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, USP10 (ubiquitin specific peptidase 10) [NCBI Gene 9100] {aka UBPO}, ZEB1 (zinc finger E-box binding homeobox 1) [NCBI Gene 6935] {aka AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, GP1BA (glycoprotein Ib platelet subunit alpha) [NCBI Gene 2811] {aka BDPLT1, BDPLT3, BSS, CD42B, CD42b-alpha, DBPLT3}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, MIR34C (microRNA 34c) [NCBI Gene 407042] {aka MIRN34C, miRNA34C, mir-34c}, ASGR1 (asialoglycoprotein receptor 1) [NCBI Gene 432] {aka ASGPR, ASGPR1, CLEC4H1, HL-1}, MIR500A (microRNA 500a) [NCBI Gene 574502] {aka MIR500, MIRN500, hsa-mir-500, hsa-mir-500a, mir-500a}, KAT5 (lysine acetyltransferase 5) [NCBI Gene 10524] {aka ESA1, HTATIP, HTATIP1, NEDFASB, PLIP, TIP}, SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021] {aka ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3}, STMN1 (stathmin 1) [NCBI Gene 3925] {aka C1orf215, LAP18, Lag, OP18, PP17, PP19}, GLUL (glutamate-ammonia ligase) [NCBI Gene 2752] {aka DEE116, GLNS, GS, PIG43, PIG59}, MIR200A (microRNA 200a) [NCBI Gene 406983] {aka MIRN200A, mir-200a}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, Gnas (GNAS complex locus) [NCBI Gene 14683] {aka 5530400H20Rik, A930027G11Rik, C130027O20Rik, GPSA, GSP, Galphas}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}
- **Diseases:** autoimmune and genetic disorders (MESH:D030342), metabolic abnormalities (MESH:D008659), ischemia (MESH:D007511), cholestatic cholangitis (MESH:D002761), hepatocyte damage (MESH:D020263), obesity (MESH:D009765), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MESH:D000077192), non-alcoholic steatohepatitis (MESH:D005235), organ failure (MESH:D009102), steatohepatitis (MESH:D005234), tumorigenesis (MESH:D063646), chronic liver injury (MESH:D056487), carcinogenic effects (MESH:D065606), jaundice (MESH:D007565), cancer (MESH:D009369), nonalcoholic steatohepatitis (MESH:D065626), chronic hepatitis C (MESH:D019698), hepatitis B and C (MESH:D006509), LF (MESH:D008103), Tumor Susceptibility Gene 101 (MESH:C562694), variceal hemorrhage (MESH:D014648), cirrhosis (MESH:D005355), hepatic inflammation (MESH:D007249), chronic hepatic disease (MESH:D006521), MASLD (MESH:D008107), hepatocyte injury (MESH:D014947), biliary atresia (MESH:D001656), mitochondrial dysfunction (MESH:D028361), PBC (MESH:D008105), HCC (MESH:D006528), PSC (MESH:D015209), fibrotic drugs (MESH:D000081015), ALD (MESH:D008108), hepatic encephalopathy (MESH:D006501), cholestatic liver injury (MESH:D017093), biliary obstruction (MESH:D001658), cholestatic liver damage (MESH:D056486), Chronic viral hepatitis (MESH:D006525), cardiovascular, neurological, metabolic, and hepatic diseases (MESH:D002318), insulin resistance (MESH:D007333), acute liver injury (MESH:D017114), toxicity (MESH:D064420), portal hypertension (MESH:D006975), ascites (MESH:D001201), viral hepatitis (MESH:D014777)
- **Chemicals:** Rose Bengal (MESH:D012395), HA (MESH:D006820), nitric oxide (MESH:D009569), water (MESH:D014867), vitamin A (MESH:D014801), glycan (MESH:D011134), rapamycin (MESH:D020123), aldosterone (MESH:D000450), ammonia (MESH:D000641), oxygen (MESH:D010100), alcohol (MESH:D000438), LUT (MESH:D047311), ROS (MESH:D017382), saponin (MESH:D012503), arsenite (MESH:C015001), flavonoid (MESH:D005419), glucose (MESH:D005947), glutamine (MESH:D005973), OCA (MESH:C464660), lipid (MESH:D008055), LPS (MESH:D008070), DSPE (MESH:C038089), bile acid (MESH:D001647), palmitate (MESH:D010168), TAA (MESH:D013853), curcumin (MESH:D003474), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (-), Erastin (MESH:C477224)
- **Species:** Hepatitis B virus (no rank) [taxon 10407], Mus musculus (house mouse, species) [taxon 10090], hepatitis C virus [taxon 11103], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), HLSC — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_8357), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), ADSC — Homo sapiens (Human), Somatic stem cell (CVCL_WG55), TH17 — Homo sapiens (Human), Lung squamous cell carcinoma, Cancer cell line (CVCL_7026), hepatic stellate — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_M102), HSC — Homo sapiens (Human), Skin squamous cell carcinoma, Cancer cell line (CVCL_2807), LX-2 — Homo sapiens (Human), Transformed cell line (CVCL_5792)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944500/full.md

## References

187 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944500/full.md

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Source: https://tomesphere.com/paper/PMC12944500