Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress

Stefan Rudloff, Mathilde Janot, Stephane Rodriguez, Kevin Dessalle, Willi Jahnen-Dechent and Uyen Huynh-Do ()
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Stefan Rudloff: Bern University Hospital
Mathilde Janot: Bern University Hospital
Stephane Rodriguez: Bern University Hospital
Kevin Dessalle: Bern University Hospital
Willi Jahnen-Dechent: RWTH Aachen University Medical Faculty
Uyen Huynh-Do: Bern University Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20832-7

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DOI: 10.1038/s41467-020-20832-7

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