Exploring the cytoprotective role of mesenchymal stem Cell-Derived exosomes in chronic liver Fibrosis: Insights into the Nrf2/Keap1/p62 signaling pathway
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Hepatic fibrosis is a common pathology present in most chronic liver diseases. Autophagy is a lysosome-mediated intracellular catabolic and recycling process that plays an essential role in maintaining normal hepatic functions. Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor responsible for the regulation of cellular anti-oxidative stress response. This study was designed to assess the cytoprotective effect of mesenchymal stem cell-derived exosomes (MSC-exos) on endothelial-mesenchymal transition (EMT) in Carbon Tetrachloride (CCL4) induced liver fibrosis. Rats were treated with 0.1 ml of CCL4 twice weekly for 8 weeks, followed by administration of a single dose of MSC-exos. Rats were then sacrificed after 4 weeks, and liver samples were collected for gene expression analyses, Western blot, histological studies, immunohistochemistry, and transmission electron microscopy. Our results showed that MSC-exos administration decreased collagen deposition, apoptosis, and inflammation. Exosomes modulate the Nrf2/Keap1/p62 pathway, restoring autophagy and Nrf2 levels through modulation of the non-canonical pathway of Nrf2/Keap1/p62. Additionally, MSC-exos regulated miR-153-3p, miR-27a, miR-144 and miRNA-34a expression. In conclusion, the present study shed light on MSC-exos as a cytoprotective agent against EMT and tumorigenesis in chronic liver inflammation.
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MSC-Exos attenuate apoptosis and oxidative stress in fibrotic rat livers through the Nrf2/Keap1/p62 pathway.
“Additionally, MSC-Exos have been shown to attenuate apoptosis and oxidative stress in fibrotic rat livers through the Nrf2/Keap1/p62 pathway [201].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [201]
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Role of Nrf2 in Methotrexate-Induced Epithelial–Mesenchymal Transition in Alveolar A549 Cells
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Flagged first, then by citations
2 of the 100 references couldn’t be matched to a known paper.
Cited by
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Yu, S., Kong, D., Lu, B., Pan, Y., Zeng, Z., Fu, Y., Zhao, Z., He, K., Tang, R., & Xia, Q. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04747-y · Cited by 22 · see citing works
Mitochondrial dysfunction in fibrotic diseases: Research progress and MSC-exos therapy
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MSCs–derived EVs protect against chemotherapy-induced ovarian toxicity: role of PI3K/AKT/mTOR axis
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Self-citationExtracellular vesicles: emerging therapeutic agents for liver fibrosis
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- Authors
- Al Saihati, H. A., Badr, O. A., Dessouky, A. A., Mostafa, O., Samir Farid, A., Aborayah, N. H., Abdullah Aljasir, M., Baioumy, B., Mahmoud Taha, N., El-Sherbiny, M., Hamed Al‑Serwi, R., Ramadan, M. M., Salim, R. F., Shaheen, D., E.M Ali, F., & Ebrahim, N.
- Affiliations
- Benha University (EG)
- Zagazig University (EG)
- Mansoura University (EG)
- Corresponding author
- Ebrahim, Nesrine
- ORCID
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2024-11
- Volume
- 141
- Pages
- 112934
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W4401813474
- Cited by
- 17
- References
- 100
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 2
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Immunopharmacology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Princess Nourah Bint Abdulrahman University (PNURSP2024R199, MHIRSP2024006)
- AlMaarefa University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- mesenchymal stem cell-derived exosomes, chronic liver fibrosis, autophagy, endothelial-to-mesenchymal transition, carbon tetrachloride-induced liver injury, miR-153-3p, miR-27a, miR-144, miR-34a, cytoprotection, oxidative stress, collagen deposition, apoptosis, liver inflammation
- MeSH terms
- Sequestosome-1 Protein, Kelch-Like ECH-Associated Protein 1, Animals, Autophagy, Carbon Tetrachloride, Liver, Liver Cirrhosis, Male, Signal Transduction, Rats, Sprague-Dawley, MicroRNAs, NF-E2-Related Factor 2, Rats, Exosomes, Mesenchymal Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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