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Kidney Week

Abstract: PO0403

The Proteomic Landscape of Liver After AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Gui, Yuan, University of Connecticut School of Medicine, Farmington, Connecticut, United States
  • Yu, Yanbao, University of Delaware, Newark, Delaware, United States
  • Zhou, Dong, University of Connecticut School of Medicine, Farmington, Connecticut, United States
Background

Acute kidney injury (AKI) was traditionally viewed as an 'innocent bystander' in various critical illnesses that reflected disease severity in the clinic. Emerging evidence suggests that AKI is an independent protagonist that may cause acute diseases in other organs such as the liver. Thus far, the mechanisms of hepatic dysfunction in patients with AKI have not been well described. We have previously characterized the kidney proteome changes after septic AKI. Here, we further described the proteomic landscape of the liver and assessed the reno-hepatic communications after septic AKI.

Methods

Cecal ligation and puncture procedure was employed to construct the sepsis-induced AKI model. A high-resolution accurate mass-based quantitative proteomics approach was applied.

Results

After septic AKI, alanine aminotransferase (ALT) levels were markedly induced in serum at day 2, while it then dropped, approaching the baseline at day 7, reflecting the process of liver damage and repair. PAS staining exhibited a consistent trend in liver morphological changes. To understand the molecular mechanisms in AKI-caused liver injury, we examined the global proteome and phosphoproteome of the liver on day 2 and day 7 after AKI using a recently developed ultrafast and economic filter-based sample processing approach. We collectively quantified a total of 1,673 proteins and 1,219 phosphosites in the liver. The principal component analyses indicated that the liver's completely distinct protein expression patterns between day 2 and day 7 after AKI. The network analyses revealed that oxidation-reduction and metabolic processes are the top changed pathways in liver injury and repair. In the meantime, we identified a wide range of differential proteins in the liver after AKI, including Cyp7b1, cyp1a2, Hemopexin, Acss2, Orm1, Steap 4, and Haptoglobin. These proteins were further validated by western blot and immunostaining. Of particular interest, Steap4, a member of the six transmembrane epithelial antigen of the prostate, was significantly upregulated in the liver but not in the kidney upon septic AKI, suggesting a tissue-specific inflammatory response.

Conclusion

Our results implied that describing the liver's proteomic landscape after AKI would help understand reno-hepatic crosstalk, and Steap4 may serve as a potential candidate to monitor AKI-caused liver injury in the clinic.

Funding

  • NIDDK Support