Integrative transcriptomic profiling of a mouse model of hypertension-accelerated diabetic kidney disease.
Diabetic kidney disease
Glomerulus
Laser-capture microdissection
Mouse model
RNAseq
Single-nucleus
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
05
05
2021
accepted:
01
09
2021
pubmed:
9
9
2021
medline:
22
3
2022
entrez:
8
9
2021
Statut:
ppublish
Résumé
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. Single-nucleus 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.
Identifiants
pubmed: 34494644
pii: 272567
doi: 10.1242/dmm.049086
pmc: PMC8560499
pii:
doi:
Substances chimiques
Renin
EC 3.4.23.15
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests F.E.S., H.M.Æ., J.C.N., T.S., M.V.Ø., K.T.G.R. and L.N.F. are employees of Gubra ApS. N.V. and J.J. are owners of Gubra ApS.
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