Fetuin-A protein distribution in mature inflamed and ischemic brain tissue

Abstract

BackgroundThe liver-derived plasma protein fetuin-A is strongly expressed during fetal life, hence its name. Fetuin-A protein is normally present in most fetal organs and tissues, including brain tissue. Fetuin-A was neuroprotective in animal models of cerebral ischemia and lethal chronic inflammation, suggesting a role beyond the neonatal period. Little is known, however, on the presence of fetuin-A in mature human brain tissue under different physiological and pathological conditions.MethodsWe studied by immunohistochemistry (IHC) the distribution of fetuin-A protein in mature human brain autopsy tissues from patients without neurological disease, patients with inflammatory brain disorders, and patients with ischemic brain lesions. To identify fetuin-A-positive cells in these tissues we co-localized fetuin-A with GFAP (astrocytes) and CD68 (macrophages, activated microglia).Results and discussionUnlike previous reports, we detected fetuin-A protein also in mature human brain as would be expected from an abundant plasma protein also present in cerebrospinal fluid. Fetuin-A immunoreactivity was increased in ischemic white matter and decreased in inflamed cerebellar tissue. Fetuin-A immunostaining was predominantly associated with neurons and astrocytes. Unlike the developing brain, the adult brain lacked fetuin-A immunostaining in CD68-positive microglia. Our findings suggest a role for fetuin-A in tissue remodeling of neonatal brain, which becomes obsolete in the adult brain, but is re-activated in damaged brain tissue. To further assess the role of fetuin-A in the mature brain, animal models involving ischemia and inflammation need to be studied.

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

“…In this regard, it has been suggested that fetuin-A plays a role in tissue remodeling during embryogenesis, its expression peaking during the transition from organogenesis and histogenesis, when cells acquire their final phenotype, but is lost thereafter 56 , 57 . Yet, recent evidence shows that fetuin-A expression is reactivated upon ischemic brain damage, aiding tissue repair 58 . In the developing kidney, prenatal hypoxia induces apoptosis 59 , 60 and was reported to cause renal vascular dysfunction 61 , 62 , giving rise to excess amounts of cellular debris that could serve as mineralization foci.…”

Exploring Molecular Mechanisms Involved in the Development of the Depression‐Like Phenotype in Interleukin‐18‐Deficient Mice

“…AHSG is secreted into the blood mainly by the liver and is also expressed in the cerebral cortex, thalamus, and hippocampus [ 45 , 46 ]. Based on previous studies, AHSG functions in the induction of inflammation and energy balance [ 47 , 48 ].…”

Tissue chaperoning—the expanded functions of fetuin-A beyond inhibition of systemic calcification

“…In the brain, Wang et al showed that fetuin-A supplementation reduced ischemic damage after permanent middle cerebral artery occlusion in rats [ 127 ]. Heinen et al also reported a reactivation of fetuin-A upon ischemic brain damage in humans, aiding tissue repair [ 39 ]. In addition to its function as vascular calcification inhibitor, the above findings and our results suggest a more general role for fetuin-A as an indirect regulator of calcification, fibrosis, inflammation, and macrophage polarization within tissues.…”