Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury
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| Název: | Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury |
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| Autoři: | Myung Yoon Kim, Tae Hyun Yoo, Dawool Han, Chulhee Choi, Jung Tak Park, Shin Wook Kang, Seonghun Kim, Jimin Park, Jong In Yook, Jae-Kwang Yoo, Nam Hee Kim, So-Hee Ahn, Seung Hyeok Han, Hyun Sil Kim, Heakyung Yoon, Cheol Hyoung Park, Bo Young Nam, Sul A Lee |
| Přispěvatelé: | 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, Kang, Shin Wook |
| Zdroj: | Kidney International. 100:570-584 |
| Informace o vydavateli: | Elsevier BV, 2021. |
| Rok vydání: | 2021 |
| Témata: | 0301 basic medicine, 0303 health sciences, ischemia-reperfusion injury, NF-ĸB signaling, apoptosis, Acute Kidney Injury, Exosomes, Inbred C57BL, Kidney, 3. Good health, Acute Kidney Injury* / etiology, Mice, Inbred C57BL, Mice, 03 medical and health sciences, acute kidney injury, NF-KappaB Inhibitor alpha, inflammation, Reperfusion Injury, exosome, Animals, Reperfusion Injury* / prevention & control, Acute Kidney Injury* / prevention & control |
| Popis: | 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. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 0085-2538 |
| DOI: | 10.1016/j.kint.2021.04.039 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/34051264 https://europepmc.org/article/MED/34051264 https://facultyopinions.com/prime/740200041 https://www.ncbi.nlm.nih.gov/pubmed/34051264 https://ir.ymlib.yonsei.ac.kr/handle/22282913/184772 https://pubmed.ncbi.nlm.nih.gov/34051264/ https://www.kidney-international.org/article/S0085-2538(21)00508-1/fulltext |
| Rights: | Elsevier Non-Commercial CC BY NC ND |
| Přístupové číslo: | edsair.doi.dedup.....374d9e50cfbeb7b74e28fd4ec54625fa |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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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| ISSN: | 00852538 |
| DOI: | 10.1016/j.kint.2021.04.039 |