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Kidney Week

Abstract: PO0202

Humanin Improves Mitochondrial Function and Alleviates Renal Tubular Injury in Lipopolysaccharide-Induced AKI

Session Information

  • AKI Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Xiao, Zhenmeng, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
  • Li, Zhilian, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
  • Dong, Wei, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
  • Chen, Yuanhan, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
  • Liang, Xinling, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
Background

Mitochondria dysfunction is increasingly recognized to be a key role in the pathogenesis of sepsis-induced AKI. Whether Humanin (HN), a well-known mitochondrial-encoded cytoprotective peptide, has similar effect in septic AKI remains unknown. We hypothesize that HN improves mitochondrial function in sepsis-induced AKI.

Methods

LPS (10mg/kg) was given to C57BL/6 mice intraperitoneally to induce murine septic AKI, and HNG (a potent analog of humanin, 1mg / kg) was injected 15 minutes later. Mice were euthanized at 24 h after LPS injection. Blood samples and kidney tissues were collected. Blood urea nitrogen was measured to evaluate renal function. Electron microscopy was used to observe mitochondrial morphology and structure. Renal inflammation( IL-1β, IL-6 and HMGB1) was evaluated by real-time PCR. The expression of PGC1-α and TFAM, which can promote mitochondrial biogenesis, was measured by real-time PCR, western bolt and immunohistochemistry.

Results

HNG significantly reduced blood urea nitrogen levels (62.10 ±3.554 mg/dl vs. 30.30±2.558 mg/dl, n=3, p<0.05). Electron microscopy showed mitochondrial damage of renal tubular epithelial cells in the LPS group, such as mitochondrial swelling and deformation and the crista disorder or disappearance. Treatment with HNG restored mitochondrial morphology and structure. Compared with LPS group, HNG reduced the renal expression of IL-1β, IL-6 and HMGB1 and significantly increased the expression of PGC1-α and TFAM in the kidney.

Conclusion

Our data showed that humanin ameliorated renal dysfunction and attenuated renal tubular injury by alleviating mitochondrial dysfunction in LPS-induced AKI, which may be associated with upregulation of PGC1-α and its downstream transcriptional factor TFAM.

Funding

  • Government Support - Non-U.S.