ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SU-OR07

Exosome-Based Delivery of Super-Repressor IκBα Ameliorates Kidney Ischemia-Reperfusion Injury

Session Information

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