The structure, biosynthesis, and biological roles of fetuin-A: A review

Abstract

Fetuin-A is a heterodimeric plasma glycoprotein containing an A-chain of 282 amino acids and a B-chain of 27 amino acid residues linked by a single inter-disulfide bond. It is predominantly expressed in embryonic cells and adult hepatocytes, and to a lesser extent in adipocytes and monocytes. Fetuin-A binds with a plethora of receptors and exhibits multifaceted physiological and pathological functions. It is involved in the regulation of calcium metabolism, osteogenesis, and the insulin signaling pathway. It also acts as an ectopic calcification inhibitor, protease inhibitor, inflammatory mediator, anti-inflammatory partner, atherogenic factor, and adipogenic factor, among other several moonlighting functions. Fetuin-A has also been demonstrated to play a crucial role in the pathogenesis of several disorders. This review mainly focuses on the structure, synthesis, and biological roles of fetuin-A. Information was gathered manually from various journals via electronic searches using PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. Studies written in English and cohort, case-control, cross-sectional, or experimental studies were considered in the review, otherwise excluded.

Dietary Supplementation with Boswellia serrata, Verbascum thapsus, and Curcuma longa in Show Jumping Horses: Effects on Serum Proteome, Antioxidant Status, and Anti-Inflammatory Gene Expression

“…Finally, PLG and AHSG (fetuin-A), which are reduced in DS-treated horses, are plasma glycoproteins, which too play a role in inflammation. Whereas PLG is a zymogen whose activation leads to the generation of plasmin, a broad-spectrum serine protease, fetuin-A functions as a carrier and multifunctional protein that participates in a wide array of essential biological activities such as regulation of bone and calcium metabolism and the insulin signaling pathway [ 86 , 87 ]. In the inflammatory response, PLG and plasmin carry out numerous functions such as intravascular and extravascular fibrinolysis, stimulation of leukocyte migration, extracellular matrix degradation, and participation in the wound healing process.…”

Fetuin-A: A Novel Biomarker of Bone Damage in Early Axial Spondyloarthritis. Results of an Interim Analysis of the SPACE Study

“…Fetuin-A is a glycoprotein produced by the liver and released into the bloodstream [ 13 ]. It is involved in several different biological processes such as the regulation of bone and calcium metabolism and the insulin signaling pathway [ 13 ]. Moreover, it has several other functions such as protease inhibitor, atherogenic, and adipogenic factors [ 13 ].…”

“…It is involved in several different biological processes such as the regulation of bone and calcium metabolism and the insulin signaling pathway [ 13 ]. Moreover, it has several other functions such as protease inhibitor, atherogenic, and adipogenic factors [ 13 ]. It has also a complex role in inflammation.…”

“…It has also a complex role in inflammation. Indeed, it has been reported that fetuin-A has both anti-inflammatory and inflammatory activity depending on the stimulus in different clinical conditions [ 13 , 14 ].…”

“…Moreover, fetuin-A is a plasma carrier protein for calcium and phosphate, regulating their levels and inhibiting ectopic calcification [ 13 , 15 ]. It has been suggested to be a potential biomarker for several diseases (i.e., depression in the elderly, coronary artery disease, metabolic syndrome, aortic valve stenosis, rheumatoid arthritis, and type 2 diabetes mellitus risk) [ 16 , 17 , 18 , 19 , 20 , 21 ].…”