Chemerin Forms: Their Generation and Activity

Abstract

Chemerin is the product of the RARRES2 gene which is secreted as a precursor of 143 amino acids. That precursor is inactive, but proteases from the coagulation and fibrinolytic cascades, as well as from inflammatory reactions, process the C-terminus of chemerin to first activate it and then subsequently inactivate it. Chemerin can signal via two G protein-coupled receptors, chem1 and chem2, as well as be bound to a third non-signaling receptor, CCRL2. Chemerin is produced by the liver and secreted into the circulation as a precursor, but it is also expressed in some tissues where it can be activated locally. This review discusses the specific tissue expression of the components of the chemerin system, and the role of different proteases in regulating the activation and inactivation of chemerin. Methods of identifying and determining the levels of different chemerin forms in both mass and activity assays are reviewed. The levels of chemerin in circulation are correlated with certain disease conditions, such as patients with obesity or diabetes, leading to the possibility of using chemerin as a biomarker.

The Role of Adipokines in the Pathogenesis of Psoriasis

“…It is synthesized as preprochemerin and processed by various members of the fibrinolytic, coagulation, and inflammatory pathways. Chemerin binds to several receptors, including chemokine-like receptor 1 (CMKLR1), known as Chemerin receptor 1, G-protein coupled receptor 1 (GPR1) also named chemerin receptor 2, and C-C chemokine receptor-like 2 (CCRL2) [ 196 ]. Various signaling pathways are considered to be stimulated, such as the AMPK, MAPK, and Akt pathways [ 197 ].…”

Crucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity

“…Chemerin is a 16 kDa adipokine secreted as an 18 kDa inactive pro-protein which can be activated by an extracellular serine protease cleavage of the C-terminal portion generating the active forms of chemerin, i.e., chem158K, chem157S and chem156F that are secreted into the bloodstream [ 21 ]. Previously, chemerin expression was found to be dramatically higher both in omental and subcutaneous adipose tissue in obesity [ 22 ].…”

Chemerin levels in chronic kidney disease: A systematic review and meta-analysis

“…The observed elevation in chemerin levels can reasonably be thought to be a result of either an increase in chemerin production or a decrease in its excretion. Chemerin is expressed throughout the body, but its production is believed to be dominated by the liver, with adrenal and pancreatic glands as additional significant sources ( 24 ). Comparatively, the expression of chemerin in the kidney is less than 5% of that in the liver ( 25 ).…”

“…Chem1, the most common chemerin receptor, is a Gi/Go protein of the G protein family, which inhibits the production of cAMP and promotes the production of IP3, calcium influx, and activation of phospholipase C, PI3 kinase, and MAPK pathways ( 28 ). Chem1 is highly expressed in the kidneys, much more so than chemerin itself, suggesting high sensitivity to chemerin produced elsewhere ( 24 ). This receptor has been shown to mediate the proinflammatory function of chemerin owing to its expression on macrophages and dendritic cells.…”