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

Rudloff, Stefan; Janot, Mathilde; Rodriguez, Stephane; Dessalle, Kevin; Jahnen-Dechent, Willi; Huynh-Do, Uyen (2021). Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress. Nature Communications, 12(1), p. 549. Springer Nature 10.1038/s41467-020-20832-7

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Rudloff, Stefan and Huynh-Do, Uyen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Prof. Dr. Uyen Huynh-Do

Date Deposited:

19 Apr 2021 11:26

Last Modified:

25 Apr 2021 03:04

Publisher DOI:

10.1038/s41467-020-20832-7

PubMed ID:

33483479

BORIS DOI:

10.7892/boris.152983

URI:

https://boris.unibe.ch/id/eprint/152983

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