Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress
Open Access
- 22 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-16
- https://doi.org/10.1038/s41467-020-20832-7
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.This publication has 101 references indexed in Scilit:
- Fetuin-A-Containing Calciprotein Particles Reduce Mineral Stress in the MacrophagePLOS ONE, 2013
- The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formationProceedings of the National Academy of Sciences of the United States of America, 2012
- Humans at high altitude: Hypoxia and fetal growthRespiratory Physiology & Neurobiology, 2011
- NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathyProceedings of the National Academy of Sciences of the United States of America, 2011
- High-resolution genome-wide mapping of HIF-binding sites by ChIP-seqBlood, 2011
- Peripheral Administration of Fetuin-A Attenuates Early Cerebral Ischemic Injury in RatsJournal of Cerebral Blood Flow & Metabolism, 2009
- Genome-wide Association of Hypoxia-inducible Factor (HIF)-1α and HIF-2α DNA Binding with Expression Profiling of Hypoxia-inducible TranscriptsOnline Journal of Public Health Informatics, 2009
- Induction of trefoil factor (TFF)1, TFF2 and TFF3 by hypoxia is mediated by hypoxia inducible factor‐1: implications for gastric mucosal healingBritish Journal of Pharmacology, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- The Human Genome Browser at UCSCGenome Research, 2002