Abstract: SU-OR07
Exosome-Based Delivery of Super-Repressor IκBα Ameliorates Kidney Ischemia-Reperfusion Injury
Session Information
- AKI Mechanisms: Research Abstracts
October 25, 2020 | Location: Simulive
Abstract Time: 05:00 PM - 07:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Lee, Sul A, Metrowest Medical Center, Framingham, Massachusetts, United States
- Kim, Seonghun, Yonsei University Dental Hospital, Seoul, Korea (the Republic of)
- Park, Jimin, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Nam, Boyoung, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Park, Jung Tak, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Han, Seung Hyeok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Kang, Shin-Wook, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Yoo, Tae-Hyun, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
Background
Ischemia-reperfusion (IR) injury (IRI) is a major cause of acute kidney injury (AKI). Recent studies on the pathophysiology of IR-induced AKI showed that immunologic responses significantly affect renal IRI and repair. Nuclear factor (NF)-κB signaling, which controls cytokine production and cell survival, is significantly involved in IR-induced AKI; its inhibition can ameliorate ischemic AKI. We assessed whether the systemic delivery of the NF-κB inhibitor using exosomes could alleviate the course of ischemic AKI.
Methods
Using EXPLOR, a novel, optogenetically engineered exosome technology, we successfully delivered the exosomal super-repressor inhibitor of NF-κB (Exo-srIκB) into B6 wildtype mice before/after kidney IR surgery, and compared outcomes with those of the control exosome (Exo-Naïve)-injected group. To better understand the protective mechanism of Exo-srIκB in renal IRI, the expression of pro-inflammatory cytokines/chemokines and adhesion molecules and the level of apoptosis were measured using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, western blot, and immunohistochemical/immunofluorescent (IF) staining. Immune cell populations of post-ischemic kidneys and spleens were analyzed using flow cytometry and IF staining.
Results
Exo-srIκB treatment resulted in lower levels of serum blood urea nitrogen (BUN), creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) in post-ischemic mice than in the Exo-Naïve treatment group (24-h/48-h BUN, creatinine, and NGAL, P < 0.001). Systemic delivery of Exo-srIκB decreased NF-κB activity in post-ischemic kidneys, leading to reduced apoptosis levels. Post-ischemic kidneys showed decreased gene expression of pro-inflammatory cytokines and adhesion molecules with Exo-srIκB treatment as compared with the control. Exo-srIκB treatment also significantly affected post-ischemic renal immune cell populations, lowering neutrophil, monocyte/macrophage, and T cell frequencies than those in the control.
Conclusion
Thus, the modulation of NF-κB signaling through exosomal delivery can be used as a novel therapeutic method for IR-induced AKI.
Funding
- Other U.S. Government Support –