Description
LECT2 (Leukocyte Cell-Derived Chemotaxin 2) is a 16 kDa secreted protein identified as a neutrophil chemotactic factor from a culture fluid of the PHA-activated human T-cell leukemia SKW-3 cells. LECT2, which is specifically expressed in the liver, is a direct target gene of Wnt/beta-catenin signaling. Beta-catenin gene (CTNNB1) mutations are one of the major oncogenic gene alterations in Hepatocellular carcinoma (HCC) which is the leading cause of cancer-related death. HCC pathogenesis is linked to liver inflammation and its oncogenic β-catenin signaling lead to deficiency in that LECT2 prohibits tumor progression by regulating Th2-based inflammation. In Lect2-deficient mice, concanavalin A-induced hepatitis is exacerbated. LECT2 regulates the homeostasis of NKT cells in the liver and be involved in the pathogenesis of hepatitis. The Val58Ile polymorphism of LECT2 is associated with the severity of rheumatoid arthritis (RA). LECT2 exerts anti-inflammatory and directly suppresses the development of collagen antibody-induced arthritis.
Recently, LECT2 is identified as a new type of amyloidogenic protein. LECT2 amyloid tends to have an affinity to kidney and liver, and is associated with renal and liver amyloidosis. LECT2 has the sequence homology with peptidase M23 structural family having a zinc ion as a cofactor (PF01551).
Self-oligomerization of the recombinant LECT2 by disulfide bonds is suppressed by addition of zinc. Therefore the LECT2 structure is stabilized by zinc.
Serum LECT2 levels are increased by obesity and fatty liver, and Lect2-deficient mice showed increased insulin sensitivity in the skeletal muscle. LECT2 plays as a hepatokine that links obesity to insulin resistance in skeletal muscle