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Kidney Week

Abstract: SA-PO186

Kidney Damage Associated with Liver Fibrosis Is Differentially Orchestrated by YB-1 Depending on Its Cellular Origin

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Liu, Xiyang, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
  • Hermert, Daniela, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
  • Leitz, Anna, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
  • Gao, Yingying, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
  • Wang, Jialin, Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China
  • Floege, Jürgen, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
  • Ostendorf, Tammo, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
  • Raffetseder, Ute, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany
Background

Acute kidney injury is a common and life-threatening complication of liver disease. In a previous study, we showed that the Y-box-binding protein (YB)-1 modulates the liver-kidney crosstalk. In a model of liver fibrosis (biliary duct ligation; BDL), mice with half-maximal Ybx1 expression (Ybx1+/-) exhibited significantly reduced liver damage, but the resulting kidney damage was increased. The purpose of the present study was to clarify the influence of organ/cell specific YB-1 expression on liver and kidney damage after induction of liver fibrosis.

Methods

For this purpose, BDL was performed as a liver fibrosis model in conditional Ybx1 knockout animals with specific depletion in hepatocytes (Ybx1flxAlfpcre), in myeloid immune cells (Ybx1flxLysMcre) and in renal tubular cells (Ybx1flxPax8cre).

Results

We found that targeting Ybx1 in hepatocytes reduced liver fibrosis and kidney damage (e.g. tubular damage, Ngal mRNA expression)/fibrosis (e.g. collagen1A staining). Compared to WT animals, BDL mice with Ybx1-specific knockout in myeloid immune cells showed significantly reduced serum levels of liver enzymes but increased evidence of kidney damage and fibrosis. Finally, decreased expression of YB-1 in kidney tubular cells resulted in increased expression of fibrosis markers in the liver.

Conclusion

In summary, cell-specific YB-1 expression has a major influence on the respective organ damage in the context of the liver-kidney crosstalk. In addition, we document that renal YB-1 expression also has implications for liver fibrosis. Furthermore, the previously observed reduced liver damage with increased kidney damage occurring in the Ybx1+/- animals is best mimicked by a specific YB-1 reduction in immune cells.

Funding

  • Government Support – Non-U.S.