Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury
Open accessAbstract
Ischemia-reperfusion injury is a major cause of acute kidney injury. Recent studies on the pathophysiology of ischemia-reperfusion-induced acute kidney injury showed that immunologic responses significantly affect kidney ischemia-reperfusion injury and repair. Nuclear factor (NF)-ĸB signaling, which controls cytokine production and cell survival, is significantly involved in ischemia-reperfusion-induced acute kidney injury, and its inhibition can ameliorate ischemic acute kidney injury. Using EXPLOR, a novel, optogenetically engineered exosome technology, we successfully delivered the exosomal super-repressor inhibitor of NF-ĸB (Exo-srIĸB) into B6 wild type mice before/after kidney ischemia-reperfusion surgery, and compared outcomes with those of a control exosome (Exo-Naïve)-injected group. Exo-srIĸB treatment resulted in lower levels of serum blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin in post-ischemic mice than in the Exo-Naïve treatment group. Systemic delivery of Exo-srIĸB decreased NF-ĸB activity in post-ischemic kidneys and reduced apoptosis. Post-ischemic kidneys showed decreased gene expression of pro-inflammatory cytokines and adhesion molecules with Exo-srIĸB treatment as compared with the control. Intravital imaging confirmed the uptake of exosomes in neutrophils and macrophages. Exo-srIĸB treatment also significantly affected post-ischemic kidney immune cell populations, lowering neutrophil, monocyte/macrophage, and T cell frequencies than those in the control. Thus, modulation of NF-ĸB signaling through exosomal delivery can be used as a novel therapeutic method for ischemia-reperfusion-induced acute kidney injury.
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Optogenetically engineered exosome technology EXPLOR delivering NF-κB inhibitors into kidney ischemia-reperfusion mice improved renal injury significantly compared with control.
“Compared with the control group, the results confirmed it could improve renal injury significantly by regulating different biological components [99].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [99]
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- Authors
- Kim, S., Lee, S. A., Yoon, H., Kim, M. Y., Yoo, J.-K., Ahn, S.-H., Park, C. H., Park, J., Nam, B. Y., Park, J. T., Han, S. H., Kang, S.-W., Kim, N. H., Kim, H. S., Han, D., Yook, J. I., Choi, C., & Yoo, T.-H.
- Affiliations
- Yonsei University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Corresponding author
- Yook, Jong In
- Choi, Chulhee
- Yoo, Tae-Hyun
- ORCID
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 100
- Issue
- 3
- Pages
- 570-584
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W3164860351
- Cited by
- 100
- References
- 52
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 23 · 2023: 27 · 2022: 9 · 2021: 3
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- exosomes, NF-κB signaling, renal ischemia-reperfusion injury, acute kidney injury, exosome delivery, neutrophil gelatinase-associated lipocalin, apoptosis, inflammatory cytokines, neutrophils, macrophages, T cells, intravital imaging
- MeSH terms
- NF-KappaB Inhibitor alpha, Animals, Kidney, Mice, Inbred C57BL, Reperfusion Injury, Mice, Exosomes, Acute Kidney Injury
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