Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.
Animals
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Calcinosis
/ genetics
Disease Models, Animal
Female
Fetal Growth Retardation
/ genetics
Fibrosis
Hypoxia
Inflammation
/ genetics
Kidney
/ metabolism
Macrophage Activation
/ genetics
Male
Mice, Inbred C57BL
Mice, Knockout
Reperfusion Injury
/ physiopathology
alpha-2-HS-Glycoprotein
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 01 2021
22 01 2021
Historique:
received:
17
05
2019
accepted:
18
12
2020
entrez:
23
1
2021
pubmed:
24
1
2021
medline:
9
2
2021
Statut:
epublish
Résumé
Intrauterine growth restriction (IUGR) is associated with reduced kidney size at birth, accelerated renal function decline, and increased risk for chronic kidney and cardiovascular diseases in adults. Precise mechanisms underlying fetal programming of adult diseases remain largely elusive and warrant extensive investigation. Setting up a mouse model of hypoxia-induced IUGR, fetal adaptations at mRNA, protein and cellular levels, and their long-term functional consequences are characterized, using the kidney as a readout. Here, we identify fetuin-A as an evolutionary conserved HIF target gene, and further investigate its role using fetuin-A KO animals and an adult model of ischemia-reperfusion injury. Beyond its role as systemic calcification inhibitor, fetuin-A emerges as a multifaceted protective factor that locally counteracts calcification, modulates macrophage polarization, and attenuates inflammation and fibrosis, thus preserving kidney function. Our study paves the way to therapeutic approaches mitigating mineral stress-induced inflammation and damage, principally applicable to all soft tissues.
Identifiants
pubmed: 33483479
doi: 10.1038/s41467-020-20832-7
pii: 10.1038/s41467-020-20832-7
pmc: PMC7822914
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
alpha-2-HS-Glycoprotein
0
endothelial PAS domain-containing protein 1
1B37H0967P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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