Cited by 101Acute Kidney Injury ResearchExtracellular vesicles in diseaseRNA Interference and Gene Delivery

Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury

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Kim, Seonghun, Lee, Sul A, Yoon, Heakyung, Kim, Myung Yoon, Yoo, Jae-Kwang, Ahn, So-Hee, Park, Cheol Hyoung, Park, Jimin +10 more·2021·Kidney International

Abstract

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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Crossref · 10.1016/j.kint.2021.04.039

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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
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
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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