Evidence mapPaperPMID 41229272Full record

ArticleAnimal models and experimental medicine2025

Temporal glomerular gene expression dynamics during disease progression in a mouse model of hypertension-accelerated diabetic kidney disease.

Adam B Marstrand-Jørgensen, Frederikke Emilie Sembach, Maria Ougaard, Ditte Hansen, Mette Viberg Østergaard, Henrik H Hansen, Louise S Dalbøge, Ole Jørgen Kaasbøll, Michael Christensen

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Article in Animal models and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Adam B Marstrand-JørgensenGubra A/S, Hørsholm, Denmark.ORCID 0009-0005-5917-3154
Frederikke Emilie SembachGubra A/S, Hørsholm, Denmark.
Maria OugaardGubra A/S, Hørsholm, Denmark.
Ditte HansenDepartment of Nephrology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
Mette Viberg ØstergaardCardiovascular & Renal Disease Therapeutic area, Novo Nordisk A/S, Måløv, Denmark.
Henrik H HansenGubra A/S, Hørsholm, Denmark.
Louise S DalbøgeGubra A/S, Hørsholm, Denmark.
Ole Jørgen KaasbøllTribune Therapeutics AS, Oslo, Norway.
Michael ChristensenGubra A/S, Hørsholm, Denmark.

Funding

Innovation Fund Denmark 2040-00034B
6 · The paper itself

Abstract

backgroundThe current understanding of diabetic kidney disease (DKD) has significant gaps regarding the underlying pathogenesis. In this study, we aimed to characterize the temporal progression of DKD using a state-of-the-art mouse model of hypertension-accelerated disease, integrating kidney biomarker analysis, histopathology, and glomerular transcriptomic profiling.

methodsFemale diabetic db/db mice received a single intravenous dose of adeno-associated virus-mediated renin overexpression (ReninAAV, week 5) and underwent uninephrectomy (UNx, week 4). db/db UNx-ReninAAV mice were terminated at weeks 1, 4, 8, and 12 (n = 7-8 per group). Female db/m mice were used as healthy controls. Study endpoints included plasma and urine biochemistry, glomerulosclerosis scoring, quantitative kidney histology, and RNA sequencing of glomeruli isolated using laser-capture microdissection.

resultsdb/db UNx-ReninAAV mice developed progressive albuminuria (from week 4) and glomerulosclerosis (from week 8). A pathway analysis of clustered gene regulations revealed broad glomerular transcriptome perturbations with signatures of increased extracellular matrix (ECM) turnover from week 8 and early onset of metabolic dysfunction. Markers of glomerular cell types and injury exhibited temporal regulation over the course of DKD, with early and sustained downregulation of endothelial markers, heterogeneous regulation of podocyte markers, and significant mesangial and parietal epithelial aberrations. Furthermore, the upregulation of cell injury markers confirmed progressive glomerular injury in the model.

conclusionThe db/db UNx-ReninAAV mouse model exhibits distinct temporal dynamics in glomerular cell markers, metabolic dysregulation, ECM remodeling, and injury. Together, these results highlight the utility of the db/db UNx-ReninAAV model as a relevant preclinical platform for studying progressive DKD.

Indexed as

Diabetic NephropathiesHypertensionKidney GlomerulusAnimalsDisease Models, AnimalDisease ProgressionFemaleMiceTranscriptomedb/db UNx‐ReninAAV mousediabetic kidney diseaseglomerular transcriptomicsglomerulosclerosislaser‐capture microdissection

Identifiers

PMID41229272
PMCPMC12884439

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.