C3 Protein

Quality Statement:
As the most abundant complement protein in the blood, complement component 3 (C3) is a key player in the complement system and a vital factor in the innate immune system. The human C3 gene (C3) is located on the short arm of chromosome 19 (19p13.3), contains 41 exons, and is highly polymorphic, suggesting that selection of C3 alleles within a population may confer differences in immune responses to various pathogens. Circulating C3 is produced primarily in the liver; however, some immune cells and non-immune cells, such as lymphocytes, neutrophils and mesenchymal cells, can also synthesize C3. C3 can be activated tonically in human CD4+ T cells through cathepsin L cleavage into C3a and C3b. C3 is highly expressed in isolated human islets, and C3-knockout β-cells exhibit increased cell death after challenge with diabetogenic stresses. Other studies have indicated that intracellular C3 protects rodent and human pancreatic β-cells from cytokine-induced apoptosis. The close correlations between complement C3 levels and obesity/IR have been reported in some researches. C3 could be an early biomarker for incident T2DM, and that BMI might play a potential mediating role in the C3-T2DM associations, which provided clues for the pathogenesis of diabetes. C3 could independently predict the development of diabetes mellitus, pre-diabetes and metabolic syndrome.

Reference:
1.Lubbers R. et al. (2017) Production of complement components by cells of the immune system. Clin Exp Immunol. 188: 183-194.2.King B C. et al. (2019) Intracellular cytosolic complement component C3 regulates cytoprotective autophagy in pancreatic beta cells by interaction with ATG16L1. Autophagy. 15: 919-921.3.Hajishengallis G. et al. (2017) Novel mechanisms and functions of complement. Nat Immunol. 18: 1288-1298.4.Ursini F. et al. (2018) The emerging role of complement C3 as a biomarker of insulin resistance and cardiometabolic diseases: preclinical and clinical evidence. Rev Recent Clin Trials. 13: 61-68.