Integrative transcriptomic profiling of a mouse model of hypertension-accelerated diabetic kidney disease

Frederikke E. Sembach, Helene M. Agidius, Lisbeth N. Fink, Thomas Secher, Annemarie Aarup, Jacob Jelsing, Niels Vrang, Bo Feldt-Rasmussen, Kristoffer T.G. Rigbolt, Jens C. Nielsen, Mette V. Østergaard*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

6 Citationer (Scopus)
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Abstract

The current understanding of molecular mechanisms driving diabetic kidney disease (DKD) is limited, partly due to the complex structure of the kidney. To identify genes and signalling pathways involved in the progression of DKD, we compared kidney cortical versus glomerular transcriptome profiles in uninephrectomized (UNx) db/db mouse models of early-stage (UNx only) and advanced [UNxplus adeno-associated virus-mediated renin-1 overexpression (UNx-Renin)] DKD using RNAseq. Compared to normoglycemic db/m mice, db/db UNx and db/db UNx-Renin mice showed marked changes in their kidney cortical and glomerular gene expression profiles. UNx-Renin mice displayed more marked perturbations in gene components associated with the activation of the immune system and enhanced extracellular matrix remodelling, supporting histological hallmarks of progressive DKD in this model. Singlenucleus RNAseq enabled the linking of transcriptome profiles to specific kidney cell types. In conclusion, integration of RNAseq at the cortical, glomerular and single-nucleus level provides an enhanced resolution of molecular signalling pathways associated with disease progression in preclinical models of DKD, and may thus be advantageous for identifying novel therapeutic targets in DKD.

OriginalsprogEngelsk
Artikelnummerdmm049086
TidsskriftDMM Disease Models and Mechanisms
Vol/bind14
Udgave nummer10
ISSN1754-8403
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
F.E.S. and H.M.Æ. were supported by grants from Innovationsfonden (8053-00140B and 8053-00051B).

Publisher Copyright:
© 2021 Company of Biologists Ltd. All rights reserved.

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