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Kidney Week

Abstract: FR-PO056

Effect of NLRP3 on Rhabdomyolysis-Induced AKI Model

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Song, Suk jong, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Lee, Sangho, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Moon, Ju young, Kyung Hee University, College of Medicine, Seoul, Korea (the Republic of)
  • Kim, Yang gyun, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Jeong, Kyung-hwan, Kyung Hee University, School of Medicine, Seoul, Korea (the Republic of)
  • Kim, Dong-Jin, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kim, Su-Mi, Kyung Hee University, Seoul, Korea (the Republic of)
  • Jung-Woo, Seo, Kyung Hee University, Seoul, Korea (the Republic of)
  • Jung, Su Woong, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Lee, Yu ho, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Seoul, Korea (the Republic of)
Background

Recent studies suggested NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome contribute renal injury in rhabdomyolysis. However, a role of the inflammasome-independent tubular epithelial NLRP3 in rhabdomyolysis-induced acute kidney injury (RAKI) has not clarified yet. We investigated the role of both inflammasome-independent tubular NLRP3 and inflammasome-dependent NLRP3 in RAKI and evaluated the possibility of NLRP3 as the treatment target of RAKI.

Methods

HK-2 cells and THP-1 cells were treated with myoglobin to mimic the rhabdomyolysis environment in vitro. A glycerol-induced rhabdomyolysis animal model was used to generate RAKI model in NLRP3 knock-out (KO) and wild-type (WT) mice.

Results

Apoptosis increased by myoglobin-induced injury in HK-2 cells; however, the number of apoptotic cells significantly decreased in siNLRP3 treated HK-2 cells. The increase of inflammatory cytokines, IL-1β and IL-18, by myoglobin-induced injury in THP-1 cells attenuated by siNLRP3 treatment. The RAKI NLRP3 KO mice showed a marked decrease in serum creatine levels, renal KIM-1, and histologic renal injury scores than in RAKI WT mice. Apoptotic markers such as PARP and cleaved caspase-3 in the kidney decreased in NLRP3 KO mice compared with WT. Also, inflammatory cytokines such as IL-6, TNF-α, and IL-1β decreased in RAKI NLRP3 KO.

Conclusion

In conclusion, the deficiency of NLRP3 protected kidneys from RAKI by both inflammasome-independent and -dependent ways. The depletion of NLRP3 directly reduced the renal tubular cell apoptosis and blocked the NLRP3 inflammasome activation of the macrophage after RAKI. Our results suggest that NLRP3 could play the essential role in RAKI and be a candidate as a treatment target.

Funding

  • Government Support - Non-U.S.