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Cited by 14Liver physiology and pathologyLiver Disease Diagnosis and TreatmentNanoparticle-Based Drug Delivery

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Biomimetic mesenchymal stem cell membrane-coated nanoparticle delivery of MKP5 inhibits hepatic fibrosis through the IRE/XBP1 pathway

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Tian, Yafei, Sun, Dandan, Liu, Na, Zhao, Jianan, Zhao, Tongjian, Liu, Xiaonan, Dong, Xinzhe, Dong, Li, Wang, Wei, Jiao, Ping, Ma, Jie·2024·Journal of Nanobiotechnology
DOI 10.1186/s12951-024-03029-8PMC PMC11606114
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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 CCl4 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.

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Metadata

Authors
Tian, Y., Sun, D., Liu, N., Zhao, J., Zhao, T., Liu, X., Dong, X., Dong, L., Wang, W., Jiao, P., & Ma, J.
Affiliations
Jilin University (CN)
Corresponding author
  • Jiao, Ping
  • Ma, Jie
ORCID
Venue
Journal of Nanobiotechnology
Publisher
Springer Science and Business Media LLC
Published
2024-11-28
Volume
22
Issue
1
Pages
741-741
ISSN
1477-3155 (ISSN-L)
DOI
10.1186/s12951-024-03029-8
PMC
PMC11606114
OpenAlex
W4404796638
Cited by
14
References
4
Citations by year
2026: 10 · 2025: 4
FWCI
3.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nanobiotechnology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Research Initiation Fund of Jilin University (419080600207)
  • Natural Science Foundation of Jilin Province (3D5242534432)
  • Jilin Province Development and Reform Commission (2022C014)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
liver fibrosis, endoplasmic reticulum stress, PLGA nanoparticles, hepatic stellate cells, hepatocyte apoptosis, carbon tetrachloride-induced liver injury, targeted drug delivery, liver inflammation
MeSH terms
X-Box Binding Protein 1, Animals, Carbon Tetrachloride, Cell Membrane, Endoribonucleases, Humans, Liver, Liver Cirrhosis, Male, Mice, Inbred C57BL, Signal Transduction, Apoptosis, Protein Serine-Threonine Kinases, Mice, Knockout, Hepatocytes, Mice, Nanoparticles, Hepatic Stellate Cells, Mesenchymal Stem Cells

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