한빛사논문
- 조회490
Seonghun Kim1,7, Sul A Lee2,3,7, Heakyung Yoon4, Myung Yoon Kim4, Jae-Kwang Yoo4, So-Hee Ahn4, Cheol Hyoung Park4, Jimin Park5, Bo Young Nam5, Jung Tak Park2, Seung Hyeok Han2, Shin-Wook Kang2, Nam Hee Kim1, Hyun Sil Kim1, Dawool Han1, Jong In Yook1, Chulhee Choi4,6 and Tae-Hyun Yoo2
1Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, South Korea; 2Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, South Korea; 3Department of Internal Medicine, MetroWest Medical Center, Framingham, Massachusetts, USA; 4ILIAS Innovation Center, ILIAS Biologics Inc., Daejeon, South Korea; 5Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul, South Korea; and 6Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea 7SK and SAL contributed equally to the manuscript.
Correspondence: Tae-Hyun Yoo or Jong In Yook or Chulhee Choi
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.
논문정보
- Research article
- 2021년 09월 (BRIC 등록일 2021-08-25)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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