Description
Fetuin-A (AHSG), a 59 kDa glycoprotein, consists of two cystatin-like domains and a smaller unrelated domain. Its homologues have been identified in several species including rat (pp63), mouse, guinea pig, rabbit, sheep, cattle, swine and human. AHSG human gene is located on chromosome 3q27. Liver synthesized fetuin-A is secreted into the blood stream and it is deposited as a noncollagenous protein in mineralized bones and teeth. Fetuin-A occurs in high serum concentration during fetal life, whereas its level declines following infection, inflammation (by 20-30% during acute phase) and malignancy. Fetuin-A may influence the resolution of inflammation by modulating the phagocytosis of apoptotic cells by macrophages. Fetuin-A acts as an important circulating inhibitor of ectopic calcification that is a frequent complication of many degenerative diseases. The low fetuin-A level may be associated with higher cardiovascular mortality in chronic renal failure, liver cancer and liver cirrhosis patients on long-term dialysis. Human fetuin-A represents a natural inhibitor of tyrosine kinase activity of the insulin receptor. Fetuin-A may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation and may be a novel therapeutic target in the treatment of type 2 diabetes, obesity, and other insulin-resistant conditions. The serum and bone-resident fetuin-A binds to transforming growth factor-β and blocks TGF-β binding to cell surface receptors. Thus, fetuin-A is involved at least in inhibition of unwanted (vascular) calcification, inhibition of insulin receptor tyrosine kinase activity and regulation of osteogenesis