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

doi:10.3390/cells12101426

Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease

Cells. 2023 May 19;12(10):1426. doi: 10.3390/cells12101426.

Authors

Affiliations

¹ Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany.
² Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig University, 04103 Leipzig, Germany.
³ Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
⁴ Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
⁵ Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, 39120 Magdeburg, Germany.
⁶ Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou 310058, China.

Abstract

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.

Keywords: cold shock proteins; kidney fibrosis; kidney injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cold-Shock Response
DNA-Binding Proteins / metabolism
Fibrosis
Kidney Diseases* / pathology
Kidney Tubules / pathology
Mice
Ureteral Obstruction* / complications
Ureteral Obstruction* / genetics

Substances

DNA-Binding Proteins
Csda protein, mouse

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG): Project-ID 97850925—SFB 854, project A01, grants ME-1365/7-2 and ME-1365/9-1 to P.R.M. and LI-1031/4-1 to J.A.L., and Project-ID 361210922—GRK 2408—(Projects 8 and 10 to P.R.M, Projects 7 and 9 to B.I.). L.P. was supported by SFB 854, project Z01. The federal state Saxony-Anhalt and the European Structural and Investment Funds (ESF, 2014-2020): project number ZS/2016/08/80645 to PRM. The ERCB-KFB was supported by the Else Kröner-Fresenius Foundation.