Exploring the cytoprotective role of mesenchymal stem Cell-Derived exosomes in chronic liver Fibrosis: Insights into the Nrf2/Keap1/p62 signaling pathway.

Autor: Al Saihati HA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Albatin, Saudi Arabia. Electronic address: hajirsh@uhb.edu.sa., Badr OA; Department of Genetics and Genetic Engineering, Faculty of Agriculture, Benha University, Egypt. Electronic address: omnia.badr@fagr.bu.edu.eg., Dessouky AA; Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, 44519 Zagazig, Egypt. Electronic address: ariguedessouky@zu.edu.eg., Mostafa O; Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Egypt. Electronic address: Ola.mostafa@fmed.bu.edu.eg., Samir Farid A; Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt. Electronic address: ayman.samir@fvtm.bu.edu.eg., Aborayah NH; Department of Clinical Pharmacology, Faculty of Medicine, Benha University, Egypt, Department of Pharmacology, Mutah University, Mutah 61710, Jordan. Electronic address: nashwa.aborayah@fmed.bu.edu.eg., Abdullah Aljasir M; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia. Electronic address: Mjasr@qu.edu.sa., Baioumy B; Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Egypt. Electronic address: bedor.bayuomi@fmed.bu.edu.eg., Mahmoud Taha N; Department of Physiology, Umm Al-Qura University, Makkah, Saudi Arabia. Electronic address: Nmati@Uqu.edu.sa., El-Sherbiny M; Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Egypt. Electronic address: msharbini@um.edu.sa., Hamed Al-Serwi R; Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia. Electronic address: rhalserwi@pnu.edu.sa., Ramadan MM; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah City, United Arab Emirates; Department of Cardiology, Faculty of Medicine, Mansoura University, Mansoura City, Egypt. Electronic address: mramadan@sharjah.ac.ae., Salim RF; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha Universit, Egypt. Electronic address: rabab.salim@fmed.bu.edu.eg., Shaheen D; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: daliashaheen@mans.edu.eg., E M Ali F; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt., Ebrahim N; Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Stem Cell Unit, Egypt. Electronic address: Nesrien.salem@fmed.bu.edu.eg.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Nov 15; Vol. 141, pp. 112934. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1016/j.intimp.2024.112934
Abstrakt: 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 (CCL 4 ) induced liver fibrosis. Rats were treated with 0.1 ml of CCL 4 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.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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