Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secretedglycoprotein that is approximately 40kDa in size that in humans is encoded by the CHI3L1gene. The name YKL-40 is derived from the three N-terminal amino acids present on the secreted form and its molecular mass. YKL-40 is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells, vascular smooth muscle cells, and hepatic stellate cells. The biological function of YKL-40 is unclear. It is not known to have a specific receptor. Its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas and asthma.
CHI3l1 is induced by a variety of cancers and in the presence of semaphorin 7A (protein) can inhibit multiple anti-tumor immune system responses. Activating an antiviral immune pathway known as the RIG-like helicase (RLH) has the ability to counter CHI3l1 induction. Cancer cells can offset RLH by stimulating NLRX1. Poly(I:C), an RNA-like molecule, can stimulate RLH activation. RLH activation can also inhibit the expression of receptor IL-13Rα2pand lmonary metastasisre. It stores NK cell accumulation and activation. It augments the expression of IFN-α/β, chemerin and its receptor ChemR23, p-cofilin, LIMK2 and PTEN and inhibiting BRAF and NLRX1 in a MAVS-dependent manner.
It is assumed that YKL-40 plays a role in cancer cell proliferation, survival, invasiveness and in the regulation of cell-matrix interactions. It is suggested that YKL-40 is a marker associated with a poorer clinical outcome in genetically defined subgroups of different tumors. YKL-40 was recently introduced into (restricted) clinical practice. A few techniques are available for its detection.
^Hakala BE, White C, Recklies AD (December 1993). "Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family". The Journal of Biological Chemistry. 268 (34): 25803–10. PMID8245017.
^Rehli M, Krause SW, Andreesen R (July 1997). "Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation". Genomics. 43 (2): 221–5. doi:10.1006/geno.1997.4778. PMID9244440.
^Bernardi D, Padoan A, Ballin A, Sartori M, Manara R, Scienza R, Plebani M, Della Puppa A (April 2012). "Serum YKL-40 following resection for cerebral glioblastoma". J. Neurooncol. 107 (2): 299–305. doi:10.1007/s11060-011-0762-7. PMID22102082.
^Johansen JS, Christensen IJ, Riisbro R, Greenall M, Han C, Price PA, Smith K, Brünner N, Harris AL (July 2003). "High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival". Breast Cancer Res. Treat. 80 (1): 15–21. doi:10.1023/A:1024431000710. PMID12889595.
Rathcke CN, Vestergaard H (2007). "YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis". Inflamm. Res. 55 (6): 221–7. doi:10.1007/s00011-006-0076-y. PMID16955240.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Kirkpatrick RB, Emery JG, Connor JR, et al. (1998). "Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages". Exp. Cell Res. 237 (1): 46–54. doi:10.1006/excr.1997.3764. PMID9417865.
Renkema GH, Boot RG, Au FL, et al. (1998). "Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages". Eur. J. Biochem. 251 (1–2): 504–9. doi:10.1046/j.1432-1327.1998.2510504.x. PMID9492324.
Johansen JS, Stoltenberg M, Hansen M, et al. (1999). "Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity". Rheumatology (Oxford). 38 (7): 618–26. doi:10.1093/rheumatology/38.7.618. PMID10461474.
Nordenbaek C, Johansen JS, Junker P, et al. (1999). "YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization". J. Infect. Dis. 180 (5): 1722–6. doi:10.1086/315050. PMID10515841.
Connor JR, Dodds RA, Emery JG, et al. (2000). "Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization". Osteoarthr. Cartil. 8 (2): 87–95. doi:10.1053/joca.1999.0276. PMID10772238.
Kronborg G, Ostergaard C, Weis N, et al. (2003). "Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease". Scand. J. Infect. Dis. 34 (5): 323–6. doi:10.1080/00365540110080233. PMID12069012.
Cintin C, Johansen JS, Christensen IJ, et al. (2002). "High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival". Cancer. 95 (2): 267–74. doi:10.1002/cncr.10644. PMID12124825.
Steck E, Breit S, Breusch SJ, et al. (2003). "Enhanced expression of the human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) in osteoarthritic cartilage". Biochem. Biophys. Res. Commun. 299 (1): 109–15. doi:10.1016/S0006-291X(02)02585-8. PMID12435396.
Steenbakkers PG, Baeten D, Rovers E, et al. (2003). "Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies". J. Immunol. 170 (11): 5719–27. doi:10.4049/jimmunol.170.11.5719. PMID12759455.
Houston DR, Recklies AD, Krupa JC, van Aalten DM (2003). "Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes". J. Biol. Chem. 278 (32): 30206–12. doi:10.1074/jbc.M303371200. PMID12775711.