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

 Seonghun Kim  ;  Sul A Lee  ;  Heakyung Yoon  ;  Myung Yoon Kim  ;  Jae-Kwang Yoo  ;  So-Hee Ahn  ;  Cheol Hyoung Park  ;  Jimin Park  ;  Bo Young Nam  ;  Jung Tak Park  ;  Seung Hyeok Han  ;  Shin-Wook Kang  ;  Nam Hee Kim  ;  Hyun Sil Kim  ;  Dawool Han  ;  Jong In Yook  ;  Chulhee Choi  ;  Tae-Hyun Yoo 
 KIDNEY INTERNATIONAL, Vol.100(3) : 570-584, 2021-09 
Journal Title
Issue Date
Acute Kidney Injury* / etiology ; Acute Kidney Injury* / prevention & control ; Animals ; Exosomes* ; Kidney ; Mice ; Mice, Inbred C57BL ; NF-KappaB Inhibitor alpha ; Reperfusion Injury* / prevention & control
NF-ĸB signaling ; acute kidney injury ; apoptosis ; exosome ; inflammation ; ischemia-reperfusion injury
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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Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Seonghun(김성훈)
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Nam, Bo Young(남보영)
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
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