Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4
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Abstract
Abstract Backgroud: Intestinal epithelial cells (IEC) contribute to regulate gut injury after intestinal isochemia/reperfusion (II/R). Exosomes are well documented to deliver bioactive molecules to recipient cells to modulate cell function. However, the role of IEC-derived exosomes in gut damage after II/R and the underlying mechanisms remains unclear. Methods IEC-derived exosomes were intravenously injected into the rats after the superior mesenteric artery occlusion for 45 min following reperfusion for 6h. The scores of gut injury, ZO-1 and IL-17A expression, TNF-α and endotoxin concentration were determined at 3 days after II/R assault. Exosomal microRNA-23a-3p and its downstream target molecule-MAP4K4 were also detected. Results Our results showed that the IEC-derived exosomes attenuated the damage of IECs after oxygen-glucose deprivation in vitro (p<0.05) and the degree of gut injury at 3 days after II/R assault in vivo (p<0.05). Injection of miR-23a-3p knockdown exosomes derived from IECs aggravated the II/R injury whereas PF-6260933, a small-molecule inhibitor of MAP4K4, was partly reversed the injuried degree by intraperitoneal injection. Underlying mechanism studies revealed that exosomal miR-23a-3p attenuated gut damage by regulating its downstream target MAP4K4. Conclusions We demonstrated that IEC-derived exosomes alleviated the II/R injury and promoted gut damage recovery via exosomal miR-23a-3p and its downstream target molecule-MAP4K4.
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Exosomal miR-23a-3p from intestinal epithelial cells knockdown intensified gut injury after intestinal ischemia/reperfusion by targeting MAP4K4.
“Research has also revealed that exosomal miR-23a-3p from intestinal epithelial cells (IECs) knockdown intensified gut injury after intestinal ischemia/reperfusion (II/R) by targeting MAP4K4 [40].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [40]
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References 30 · Cited by 23
Research works printed but not linked: 3
- Z.Y. Wang, R.M. Sun, G.Z. Wang, Z.C. Chen, Y. Li, Y. Zhao, D.S. Liu, H.Y. Zhao, F. Zhang, J.H. Yao, X.F. Tian, SIRT3-mediated deacetylation of PRDX3 alleviates mitochondrial oxidative damage and apoptosis induced by intestinal ischemia/ reperfusion injury, Redox Biol. 28 (2020), 101343.
- G. Akbari, Emerging roles of microRNAs in intestinal ischemia/reperfusion- induced injury: a review, J. Physiol. Biochem. 76 (4) (2020) 525-537.
- L.X. Li, L.H. Yin, M. Gao, L.N. Xu, Y. Qi, J.Y. Peng, MiR-23a-5p exacerbates intestinal ischemia-reperfusion injury by promoting oxidative stress via targeting PPAR alpha, Biochem. Pharm. 180 (2020), 114194.
- Authors
- Yang, J., Zheng, X. G., Wu, Y. L., Wang, A. P., Wang, C. H., Chen, W. X., Zhong, S., & Yang, H.
- Affiliations
- Army Medical University (CN)
- Nanjing Children's Hospital (CN)
- Corresponding author
- Zhong, Shan
- Yang, Hui
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 149
- Pages
- 112810
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4220737326
- Cited by
- 23
- References
- 30
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 4 · 2023: 3 · 2022: 1
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Third Military Medical University (SKLKF202006)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Surgery › Abdominal vascular conditions and treatments
- Keywords
- exosomes, intestinal epithelial cells, MAP4K4, intestinal ischemia-reperfusion injury, gut damage, oxygen-glucose deprivation, exosomal microRNA delivery
- MeSH terms
- Animals, Epithelial Cells, Glucose, Ischemia, Oxygen, Reperfusion, Reperfusion Injury, MicroRNAs, Rats, Exosomes
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