α-Klotho (Alpha Klotho) was identified as an extremely down-regulated gene in the genetically-modified mouse of which phenotype is very similar to various symptoms of human aging. The sequences of Alpha Klotho genes have been identified in various species including humans based on the one of mouse. Alpha Klotho protein is a 130 kDa, one-transmembrane protein and its expression is confirmed in the kidneys and the parathyroid glands. In recent years, it has become clear that Alpha Klotho is an important molecule within a living organism regulating the metabolism of mineral such as calcium and phosphorus. It is considered that in Alpha Klotho mouse, early aging-like symptoms are induced by impaired mineral homeostasis caused by decreased expression of Alpha Klotho. Meanwhile, it is reported that the long N-terminal extracellular domain which comprises the major portion of sequence of Alpha Klotho protein is released free into blood by shedding. However, there are many unclear points about functions and changes in concentration of free (soluble) Alpha Klotho protein, so it was required to develop the measurement system of Alpha Klotho.
Galactose-deficient IgA1 (Gd-IgA1) attracts a lot of attentions as a critical effector molecule in the pathogenesis and progression of IgA nephropathy (IgAN) in recent studies. It has been suggested that several O-link glycans modified regions exist in the heavy chain hinge region of human IgA1 molecule andGd-IgA1 circulates in blood stream of the patients with the pathological condition of IgAN. The measuring system using snail (helix aspersa; HAA) lectin that is extracted from snail has been used in past numerous studies and it was revealed that serum levels of Gd-IgA1 in patients with IgAN is significantly elevated compared with the level of healthy subjects or patients with renal diseases other than IgAN. Thus, the importance and purpose of measuring serum Gd-IgA1 level have been gradually recognized from such studies.
However, since the measuring system used HAA lectin is not suitable for measuring multiple and massive samples in large scale studies due to its instability of glycan-recognizing activity, development of alternative measuring system that can quantitatively measure human Gd-IgA1 in serum with stable and reliable data has been considered as an essential and urgent matter. This IBL ELISA kit using the monoclonal antibody that specifically recognizes galactose-deficient hinge sequence of human Gd-IgA1 is a lectin non-dependent measuring system that can quantitatively measure Gd-IgA1 in human serum,which is also suitable for large scale studies because of its stability.
Osteopontin (OPN) is a secretory glycoprotein first isolated from the bone. At present, it is known as a highly acidic calcium-binding phosphorylated protein with sugar chain bonds, that is secreted from diverse cells, including osteoblasts, renal tubular cells, macrophages, activated T lymphocytes and vascular smooth muscle cells. Its molecular weight can vary depending on the sugar chain formation and phosphorylation, and has been reported to range from 44 to 66 kDa. One major characteristic of OPN is that its molecule contains an Arg-Gly-Asp (RGD) amino acid sequence. This motif is also seen in fibronectin, vitronectin and other extracellular proteins. It is known that OPN binds through this motif to members of the integrin family (e.g., αvβ3) of cell surface receptors. Another unique characteristic of OPN is that it can assume various molecular forms in vivo by undergoing RNA splicing, saccharification, phosphorylation, sulfation, degradation by protease, etc. OPN is considered to coexist with thrombin locally in tissues such as injured tissue, inflamed tissue, vascularized tissue, and tumor tissue. Coexistence with thrombin increases the likelihood of proteolysis, and this process may have an important physiological role. The cleavage of OPN with thrombin causes the hidden sequence of the adhering sites to be exposed. It has been reported that the fragments of OPN produced following cleavage by thrombin react with α9β1 integrin. Furthermore, in view of the finding that OPN has many cell-binding sites and can react with various receptors, interactions between OPN and these cells or receptors may play some unknown roles. This kit can specifically measure the N-terminal OPN fragment (hereinafter called “OPN N-Half”) cleaved by thrombin. OPN molecules without thrombin cleavage, on the other hand, are hardly detected by the kit.
c-Met, the product of c-met gene has been reported to be the HGF receptor since HGF induces phosphorylation of c-Met by binding specifically to it. It is a heterodimer protein composed of an α-chain that is linked to a β-chain. The β-chain has the intracellular tyrosine kinase domain, the transmembrane domain and the extracellular domain, and it is tied into the α-chain that is the extracellular domain of c-Met. c-Met exists mainly in epidermal cells. It is found in the digestive tract, prostate gland, seminal vesicles, mammary gland, microglia cells, monocytes and macrophages, and more amount in the liver and kidney. It is considered that c-Met tansmits signals resulting from binding to HGF, such as growth, motility and organ formation, in the organs and cells mentioned above. This kit is designed to measure Human c-Met.