Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease
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Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease. / Lindquist, Jonathan A; Bernhardt, Anja; Reichardt, Charlotte; Sauter, Eva; Brandt, Sabine; Rana, Rajiv; Lindenmeyer, Maja T; Philipsen, Lars; Isermann, Berend; Zhu, Cheng; Mertens, Peter R.
in: CELLS-BASEL, Jahrgang 12, Nr. 10, 1426, 19.05.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease
AU - Lindquist, Jonathan A
AU - Bernhardt, Anja
AU - Reichardt, Charlotte
AU - Sauter, Eva
AU - Brandt, Sabine
AU - Rana, Rajiv
AU - Lindenmeyer, Maja T
AU - Philipsen, Lars
AU - Isermann, Berend
AU - Zhu, Cheng
AU - Mertens, Peter R
PY - 2023/5/19
Y1 - 2023/5/19
N2 - 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.
AB - 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.
KW - Animals
KW - Mice
KW - Cold-Shock Response
KW - DNA-Binding Proteins/metabolism
KW - Fibrosis
KW - Kidney Diseases/pathology
KW - Kidney Tubules/pathology
KW - Ureteral Obstruction/complications
U2 - 10.3390/cells12101426
DO - 10.3390/cells12101426
M3 - SCORING: Journal article
C2 - 37408260
VL - 12
JO - CELLS-BASEL
JF - CELLS-BASEL
SN - 2073-4409
IS - 10
M1 - 1426
ER -