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Kidney Week

Abstract: TH-PO003

Role of NLRP3 in Rhabdomyolysis-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Cho, Won-Hee, Kyung Hee University Hospital, Gang-Dong, Seoul, Korea (the Republic of)
  • Jung, Su Woong, Kyung Hee University Hospital, Gang-Dong, Seoul, Korea (the Republic of)
  • Jeong, Kyung hwan, Kyung Hee University, College of Medicine, Seoul, Korea (the Republic of)
  • Moon, Ju young, Kyung Hee University Hospital, Gang-Dong, Seoul, Korea (the Republic of)
  • Lee, Sangho, Kyung Hee University Hospital, Gang-Dong, Seoul, Korea (the Republic of)
  • Kim, Yang gyun, Kyung Hee University Hospital, Gang-Dong, Seoul, Korea (the Republic of)
Background

NOD-like receptor, pyrin domain containing-3 (NLRP3) has been suggested to contribute to various kidney through inflammasome-depedent or –independent pathways. Recent evidence showed the association of NLRP3 inflammasome in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI); However, underlying mechanisms was not clarified yet. We investigated the role of NLRP3 in RAKI and evaluated the possibility of NLRP3 as the treatment target of RIAKI.

Methods

HK-2 cells and THP-1 cells were treated with ferrous myoglobin to mimic the rhabdomyolysis environment in vitro. A glycerol was injected intramuscularly to the gluteal area of the mice to generate RIAKI model in NLRP3 KO and WT ones. Selective NLRP3 inhibitor (MCC950) was used as a therapeutic agent.

Results

NLRP3 KO mice showed a marked decrease in serum creatinine, KIM-1, and tubular injury compared with WT mice although muscular injury was not different. Apoptosis markers and inflammatory cytokines, which were increased in the kidneys of WT mice, were mitigated in the kidneys of NLR3 KO mice. AKI was attenuated by the MCC950 treatment before glycerol injection. Ferrous myoglobin caused to increase apoptotic signals and to translocate NLRP3 from cytoplasm to mitochondria in HK-2 cells. NLRP3 knock down HK-2 cells identified significant decrease of apoptosis. Also, ferrous myoglobin activate NLRP3 inflammasome in THP-1 cells. Cleaved IL-1β was reduced in siNLRP3 treated THP-1 cells.

Conclusion

The deficiency of NLRP3 protected kidneys from RAKI by both inflammasome-independent and -dependent ways. NLRP3 could play the essential role in RIAKI and and be a candidate as a treatment target.

Funding

  • Private Foundation Support