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Biomimetic mesenchymal stem cell membrane-coated nanoparticle delivery of MKP5 inhibits hepatic fibrosis through the IRE/XBP1 pathway.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2024 Nov 28; Vol. 22 (1), pp. 741. Date of Electronic Publication: 2024 Nov 28. - Publication Year :
- 2024
-
Abstract
- Hepatic fibrosis is a common disease with high morbidity and mortality rates. The complex and poorly understood mechanisms underlying hepatic fibrosis represent a significant challenge for the development of more effective therapeutic strategies. MKP5 is a potential regulator of multiple fibrotic diseases. However, its precise role and mechanism of action in hepatic fibrosis remains unclear. This study identified a reduction in MKP5 expression in fibrotic liver tissues of mice treated with CCl <subscript>4</subscript> and observed that MKP5 knockout mice exhibited a more pronounced development of hepatic fibrosis. In addition, RNA-seq data indicated activation of protein processing in the endoplasmic reticulum signalling pathway in fibrotic liver tissues of mice lacking MKP5. Mechanistically, MKP5 inhibits the activation of hepatic stellate cells (HSCs) and hepatocyte apoptosis through the regulation of the IRE/XBP1 pathway. Based on these findings, we developed PLGA-MKP5 nanoparticles coated with a mesenchymal stem cell membrane (MSCM). Our results demonstrated that MSCM-PLGA-MKP5 was most effective in attenuating hepatic inflammation and fibrosis in murine models by modulating the IRE/XBP1 axis. This study contributes to the current understanding of the pathogenesis of hepatic fibrosis, suggesting that the targeted delivery of MKP5 via a nano-delivery system may represent a promising therapeutic approach to treat hepatic fibrosis.<br />Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were conducted in accordance with the Guidelines for Experimental Animals of Jilin University and approved by the Animal Experiment Ethics Committee of Jilin University (approval number: 20240038). Consent for publication: All authors have reviewed and agreed to the published version of the manuscript. Competing interests: The authors declare no competing interests.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Mice, Inbred C57BL
Male
Carbon Tetrachloride
Hepatic Stellate Cells metabolism
Cell Membrane metabolism
Protein Serine-Threonine Kinases metabolism
Liver metabolism
Liver pathology
Hepatocytes metabolism
Humans
Apoptosis drug effects
Endoribonucleases
X-Box Binding Protein 1 metabolism
Liver Cirrhosis metabolism
Nanoparticles chemistry
Mesenchymal Stem Cells metabolism
Mice, Knockout
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 39609656
- Full Text :
- https://doi.org/10.1186/s12951-024-03029-8