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

Xiyang Liu,

• Hermert, Daniela, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany

Daniela Hermert,

• Leitz, Anna, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany

Anna Leitz,

• Gao, Yingying, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany

Yingying Gao,

• Wang, Jialin, Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China

Jialin Wang,

• Floege, Jürgen, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany

Jürgen Floege,

• Ostendorf, Tammo, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany

Tammo Ostendorf,

• Raffetseder, Ute, Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany

Ute Raffetseder,

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 (Ybx1^flxAlfp^cre), in myeloid immune cells (Ybx1^flxLysM^cre) and in renal tubular cells (Ybx1^flxPax8^cre).

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.