Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease
Jonathan A. Lindquist,
Anja Bernhardt,
Charlotte Reichardt,
Eva Sauter,
Sabine Brandt,
Rajiv Rana,
Maja T. Lindenmeyer,
Lars Philipsen,
Berend Isermann,
Cheng Zhu,
Peter R. Mertens
Affiliations
Jonathan A. Lindquist
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
Anja Bernhardt
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
Charlotte Reichardt
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
Eva Sauter
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
Sabine Brandt
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
Rajiv Rana
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig University, 04103 Leipzig, Germany
Maja T. Lindenmeyer
Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Lars Philipsen
Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, 39120 Magdeburg, Germany
Berend Isermann
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig University, 04103 Leipzig, Germany
Cheng Zhu
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
Peter R. Mertens
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
DNA-binding protein A (DbpA) belongs to the Y-box family of cold shock domain proteins that exert transcriptional and translational activities in the cell via their ability to bind and regulate mRNA. To investigate the role of DbpA in kidney disease, we utilized the murine unilateral ureter obstruction (UUO) model, which recapitulates many features of obstructive nephropathy seen in humans. We observed that DbpA protein expression is induced within the renal interstitium following disease induction. Compared with wild-type animals, obstructed kidneys from Ybx3-deficient mice are protected from tissue injury, with a significant reduction in the number of infiltrating immune cells as well as in extracellular matrix deposition. RNAseq data from UUO kidneys show that Ybx3 is expressed by activated fibroblasts, which reside within the renal interstitium. Our data support a role for DbpA in orchestrating renal fibrosis and suggest that strategies targeting DbpA may be a therapeutic option to slow disease progression.
