# Understanding the Mechanisms of Human Liver Regeneration via Characterization of Circulating Extracellular Vesicles

**Authors:** Yilin Sun, Elisa Pasini, Anh Thu Nguyen-Lefebvre, Mamatha Bhat

PMC · DOI: 10.1155/bmri/3824534 · BioMed Research International · 2026-03-08

## TL;DR

This study explores how small extracellular vesicles and their miRNA content in blood relate to liver regeneration in humans and mice, suggesting potential noninvasive biomarkers.

## Contribution

The study identifies miRNA profiles in extracellular vesicles as potential noninvasive biomarkers for liver regeneration.

## Key findings

- Twenty-five differentially expressed miRNAs were found in human plasma during liver regeneration.
- Bioinformatic analysis linked these miRNAs to key regenerative pathways like the Hippo and cell cycle.
- Mouse plasma samples revealed 30 differentially expressed miRNAs with similar pathway associations.

## Abstract

Our study is aimed at identifying circulating extracellular vesicles associated with liver regeneration in humans and mice, exploring their roles, and evaluating their content as potential biomarkers of regeneration.

Plasma samples were collected from 12 human liver transplant recipients and 22 mice at distinct time points postsurgery, corresponding to regenerating and nonregenerating phases. Small extracellular vesicles were isolated from plasma, and miRNA was extracted for analysis using NanoString technology. To understand the role of miRNAs in liver regeneration, we utilized bioinformatics tools, including mirDIP and STRING, to identify target genes involved in regenerative signaling pathways, focusing on the Hippo and cell cycle pathways.

Twenty‐five differentially expressed miRNAs were identified from human patient plasma samples and 30 from mouse plasma samples. Bioinformatic analysis revealed a significant overlap between the predicted target genes of these miRNAs and genes involved in critical regenerative pathways, such as the cell cycle and Hippo signaling, suggesting that these miRNAs play important regulatory roles during liver regeneration.

The miRNA profiles associated with small extracellular vesicles have the potential to serve as noninvasive biomarkers for liver regeneration. Further validation of these miRNA‐based biomarkers could advance diagnostic and therapeutic approaches for liver injury and posttransplant recovery.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, RIPK3 (receptor interacting serine/threonine kinase 3) [NCBI Gene 11035] {aka RIP3}, MIR31 (microRNA 31) [NCBI Gene 407035] {aka MIRN31, hsa-mir-31, miR-31}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Brca1 (breast cancer 1, early onset) [NCBI Gene 12189], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Ywhab (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide) [NCBI Gene 54401] {aka 1300003C17Rik, 14-3-3b}, Cd81 (CD81 antigen) [NCBI Gene 12520] {aka Tapa-1, Tapa1, Tspan28}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Tsg101 (tumor susceptibility gene 101) [NCBI Gene 22088] {aka CC2}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, Yap1 (yes-associated protein 1) [NCBI Gene 22601] {aka Yap, Yap65, Yki, Yorkie}, E2f1 (E2F transcription factor 1) [NCBI Gene 13555] {aka E2F-1, Tg(Wnt1-cre)2Sor, mKIAA4009}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, Mob1a (MOB kinase activator 1A) [NCBI Gene 232157] {aka 4022402H07Rik, MOB1, MOB4B, Mobk1b, Mobkl1b}, Amot (angiomotin) [NCBI Gene 27494] {aka CAG-2, D0Kist1, Sii6}, CABIN1 (calcineurin binding protein 1) [NCBI Gene 23523] {aka CAIN, KB-318B8.7, PPP3IN}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, E2F1 (E2F transcription factor 1) [NCBI Gene 1869] {aka E2F-1, RBAP1, RBBP3, RBP3}, Th (tyrosine hydroxylase) [NCBI Gene 21823], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Cd9 (CD9 antigen) [NCBI Gene 12527] {aka Tspan29}, CCNE2 (cyclin E2) [NCBI Gene 9134] {aka CYCE2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, RIPK1 (receptor interacting serine/threonine kinase 1) [NCBI Gene 8737] {aka AIEFL, IMD57, RIP, RIP-1, RIP1}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, Ccne2 (cyclin E2) [NCBI Gene 12448], MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, Cd63 (CD63 antigen) [NCBI Gene 12512] {aka ME491, Tspan30}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}
- **Diseases:** hepatocellular carcinoma (MESH:D006528), Ischemia (MESH:D007511), UHN (MESH:C563594), PH (MESH:D004828), LDLT (MESH:D017093), hepatic injury (MESH:D056486), /R (MESH:C580424), Cancer (MESH:D009369), MISEV (MESH:C535509), acute liver failure (MESH:D017114), Liver cirrhosis (MESH:D008103), I/R) injury (MESH:D015427), fibrosis (MESH:D005355), inflammation (MESH:D007249), RPMI (MESH:D013341), liver disease (MESH:D008107), alcoholic cirrhosis (MESH:D008104), cirrhotic (MESH:D000094724)
- **Chemicals:** SDS (MESH:D012967), PVDF (MESH:C024865), PBS (MESH:D007854), formalin (MESH:D005557), ethanol (MESH:D000431), polystyrene (MESH:D011137), prednisone (MESH:D011241), CO2 (MESH:D002245), water (MESH:D014867), ethane (MESH:D004980), amylamine (MESH:C005264), Ponceau S (MESH:C032756), latex (MESH:D007840), isoflurane (MESH:D007530), lipid (MESH:D008055), Chloroform (MESH:D002725), nitrogen (MESH:D009584), EDTA (MESH:D004492), bilirubin (MESH:D001663), polyacrylamide (MESH:C016679), carbon (MESH:D002244), Triton X-100 (MESH:D017830), Cl (MESH:D002713), TCA (MESH:D014238), sodium deoxycholate (MESH:D003840), NaCl (MESH:D012965), gold (MESH:D006046), Acid-Phenol (-), mycophenolate mofetil (MESH:D009173), cyclosporine (MESH:D016572), tacrolimus (MESH:D016559)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** L120C
- **Cell lines:** /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062)

## Full text

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## Figures

16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12968334/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12968334/full.md

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Source: https://tomesphere.com/paper/PMC12968334