In 1998, Tatemoto et al. first isolated apelin from bovine stomach extracts. Apelin is an endogenous peptide ligand for the orphan G-protein-coupled angiotensin receptor-like protein J (APJ) receptor. It is widely distributed in various organs such as the lung, kidney, liver, heart, gastrointestinal tract, and adipose tissue, etc. And it was identified as a novel adipocytokine in 2005.
Apelin has many subtypes, including Apelin-36, Apelin-31, Apelin-28, Apelin-19, Apelin-13, and Apelin-12, etc., among which Apelin-36 is the main form of endogenous Apelin. And it exerts extensive functions in the human body, including the control of blood pressure and blood flow, the stimulation of cardiac contractility, the regulation of water and food intake, adipocyte differentiation, the involvement in glucose uptake and participation in the control of glucose blood levels glycemia.
Apelin signaling pathway refers to the way by which apelin binds to its cognate receptor APJ, thereby mediating the occurrence of multiple signaling pathways that involve in many cellular processes.
In the apelin signaling pathway, apelin is activated by its cognate APJ receptor, triggering a diversity of physiological effects such as vasoconstriction and dilation, the control of blood pressure and blood flow, strengthening of cardiac contractility, angiogenesis, and modulation of energy metabolism and fluid homeostasis.
Apelin exerts its physiologic and pathophysiologic functions through the interaction with its receptor APJ, in the autocrine or paracrine pathway.
Apelin and APJ are found to be highly expressed in various peripheral tissues, especially in the blood vessels, indicating that apelin/APJ plays an important role in angiogenesis and vascular formation. Apelin acts on and activates the APJ receptor. Activated APJ combines with Gi protein and PKC, phosphorylation of p70 S6 kinase through the extracellular signal-regulated kinase (ERK) pathway. Apelin/APJ signaling also activates the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, facilitating endothelial cell migration. Active Akt stimulates the phosphorylation of p70 S6 kinase. Both cell events ultimately promote the proliferation of vascular smooth muscle cells. Liu C et al. also confirmed that this signaling pathway inhibits the apoptosis of vascular smooth muscle cells.
The apelin/APJ pathway mediates the opposite effects to the renin-angiotensin system (RAS) in many physiologic and pathophysiologic conditions. Angiotensin II elevates vascular tone and raises blood pressure, whereas apelin acts as a vasodilator and lowers blood pressure. Many studies have demonstrated that intravenous injection of exogenous apelin can cause decreased systolic and diastolic blood pressure. Apelin binds to and activates APJ, stimulating Akt to activate phosphorylation of endothelial nitric oxide synthase (eNOS). The phosphorylation of eNO promotes the release of NO by endothelial cells. NO increases cGMP by activating ornithylacine cyclase in smooth muscle, which further relaxes vascular smooth muscle and lowers blood pressure, leading to vasodilatation.
The apelin signaling pathway also inhibits adipogenesis through the MAPK pathway and suppresses basal lipolysis through AMP-activated protein kinase-dependent enhancement of perilipin expression.
Apelin is involved in the pathogenesis of many diseases such as heart failure, coronary heart disease, diabetes, lung diseases, and cancer.
Studies have shown that apelin levels increase in the early stage of heart failure but disease in the late stage. In patients with type II diabetes, plasma apelin concentrations are increased. In the study of osteoarthritis (OA), apelin was found in the synovial fluid of osteoarthritis. And its concentration was positively correlated with the severity of OA, suggesting that apelin played a certain role in the occurrence or development of OA. It provides a new perspective on OA pathology.
Apelin has been reported to be widely expressed in endothelial cells of tumors of different origins. And apelin has been identified as a tumor endothelial-specific gene through the gene expression profiles comparison between tumor and normal endothelium.
|KLF2||KLF2 Antibody||KLF2 Protein||KLF2 cDNA||KLF2 ELISA Kit|
|KRAS||KRAS Antibody||KRAS Protein||KRAS cDNA||KRAS ELISA Kit|
|LIPE||LIPE Antibody||LIPE Protein||LIPE cDNA||LIPE ELISA Kit|
|MAP2K1||MAP2K1 Antibody||MAP2K1 Protein||MAP2K1 cDNA||MAP2K1 ELISA Kit|
|MAP2K2||MAP2K2 Antibody||MAP2K2 Protein||MAP2K2 cDNA||MAP2K2 ELISA Kit|
|MAPK1||MAPK1 Antibody||MAPK1 Protein||MAPK1 cDNA||MAPK1 ELISA Kit|
|MAPK3||MAPK3 Antibody||MAPK3 Protein||MAPK3 cDNA||MAPK3 ELISA Kit|
|MEF2A||MEF2A Antibody||MEF2A Protein||MEF2A cDNA||MEF2A ELISA Kit|
|MEF2B||MEF2B Antibody||MEF2B Protein||MEF2B cDNA||MEF2B ELISA Kit|
|MEF2C||MEF2C Antibody||MEF2C Protein||MEF2C cDNA||MEF2C ELISA Kit|
|MEF2D||MEF2D Antibody||MEF2D Protein||MEF2D cDNA||MEF2D ELISA Kit|
|MRAS||MRAS Antibody||MRAS Protein||MRAS cDNA||MRAS ELISA Kit|
|MTOR||MTOR Antibody||MTOR Protein||MTOR cDNA||MTOR ELISA Kit|
|MYL2||MYL2 Antibody||MYL2 Protein||MYL2 cDNA||MYL2 ELISA Kit|
|MYL3||MYL3 Antibody||MYL3 Protein||MYL3 cDNA||MYL3 ELISA Kit|
|MYL4||MYL4 Antibody||MYL4 Protein||MYL4 cDNA||MYL4 ELISA Kit|
|MYLK||MYLK Antibody||MYLK Protein||MYLK cDNA||MYLK ELISA Kit|
|MYLK2||MYLK2 Antibody||MYLK2 Protein||MYLK2 cDNA||MYLK2 ELISA Kit|
|MYLK3||MYLK3 Antibody||MYLK3 Protein||MYLK3 cDNA||MYLK3 ELISA Kit|
|MYLK4||MYLK4 Antibody||MYLK4 Protein||MYLK4 cDNA||MYLK4 ELISA Kit|