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Gene Review

CHI3L1  -  chitinase 3-like 1 (cartilage glycoprotein...

Homo sapiens

Synonyms: 39 kDa synovial protein, ASRT7, CGP-39, Cartilage glycoprotein 39, Chitinase-3-like protein 1, ...
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Disease relevance of CHI3L1


High impact information on CHI3L1


Chemical compound and disease context of CHI3L1


Biological context of CHI3L1

  • Thus HC-gp39 initiates a signalling cascade in connective-tissue cells which leads to increased cell proliferation, suggesting that this protein could play a major role in the pathological conditions leading to tissue fibrosis [3].
  • Phosphorylation of both extracellular signal-regulated kinases 1/2 and AKT occurred in a dose- and time-dependent fashion upon addition of HC-gp39 [3].
  • To allow further investigations of its unique expression pattern and to facilitate studies on the regulation of this "marker gene," we characterized the genomic organization of the HC gp-39 gene (HGMW-approved symbol CHI3L1) and cloned its 5'-proximal promotor region [10].
  • In contrast, the protective TTG haplotype was associated with a high level of CHI3L1 expression [11].
  • Third, we found that an allele of SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 by altering the transcriptional-factor consensus sequences, and this may be responsible for the decreased expression of the CCC haplotype [11].

Anatomical context of CHI3L1

  • Thus, induction and continued secretion of CHI3L1 in chondrocytes require sustained activation of NF-kappaB [1].
  • Selective induction of CHI3L1 by cytokines acting through NF-kappaB coupled with the known restriction of the catabolic responses by CHI3L1 in response to these inflammatory cytokines represents a key regulatory feedback process in controlling connective tissue turnover [1].
  • gp38k (CHI3L1) is a secreted heparin-binding glycoprotein whose expression, in vitro, is associated with vascular smooth muscle cell (VSMC) migration and invasion into the underlying gelatinous matrix. gp38k is expressed at high levels in postconfluent "nodular" VSMC cultures and at low levels in subconfluent proliferating cultures [12].
  • We report here that HC-gp39 promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts [3].
  • A dose-dependent growth stimulation was observed when each of the fibroblastic cell lines was exposed to HC-gp39 in a concentration range from 0.1 to 2 nM, which is similar to the effective dose of the well-characterized mitogen, insulin-like growth factor-1 [3].

Associations of CHI3L1 with chemical compounds

  • In these patients, high serum YKL-40 was a stronger predictor of survival than high serum HER2 or lack of estrogen receptors [2].
  • Functional Variants in the Promoter Region of Chitinase 3-Like 1 (CHI3L1) and Susceptibility to Schizophrenia [11].
  • In contrast, expression of YKL-40 was induced by IFNgamma and suppressed by dexamethasone [13].
  • In contrast to YKL-40, YKL-39 is not a glycoprotein and does not bind to heparin [14].
  • Furthermore, HC gp-39 expression levels correlate with the degree of morphological differentiation induced by PMA and vitamin D3 treatments [15].
  • Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis [16].

Physical interactions of CHI3L1


Co-localisations of CHI3L1

  • YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase in subcellular fractionation studies on stimulated and unstimulated neutrophils [18].

Regulatory relationships of CHI3L1


Other interactions of CHI3L1


Analytical, diagnostic and therapeutic context of CHI3L1


  1. Inflammatory cytokines induce production of CHI3L1 by articular chondrocytes. Recklies, A.D., Ling, H., White, C., Bernier, S.M. J. Biol. Chem. (2005) [Pubmed]
  2. High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. Jensen, B.V., Johansen, J.S., Price, P.A. Clin. Cancer Res. (2003) [Pubmed]
  3. The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Recklies, A.D., White, C., Ling, H. Biochem. J. (2002) [Pubmed]
  4. Characterization of free-floating spheres from human trabecular meshwork (HTM) cell culture in vitro. Gonzalez, P., Epstein, D.L., Luna, C., Liton, P.B. Exp. Eye Res. (2006) [Pubmed]
  5. YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Hormigo, A., Gu, B., Karimi, S., Riedel, E., Panageas, K.S., Edgar, M.A., Tanwar, M.K., Rao, J.S., Fleisher, M., DeAngelis, L.M., Holland, E.C. Clin. Cancer Res. (2006) [Pubmed]
  6. A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection. Berres, M.L., Papen, S., Pauels, K., Schmitz, P., Zaldivar, M.M., Hellerbrand, C., Mueller, T., Berg, T., Weiskirchen, R., Trautwein, C., Wasmuth, H.E. J. Hepatol. (2009) [Pubmed]
  7. Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells. Mizoguchi, E. Gastroenterology (2006) [Pubmed]
  8. YKL-40 in giant cells and macrophages from patients with giant cell arteritis. Johansen, J.S., Baslund, B., Garbarsch, C., Hansen, M., Stoltenberg, M., Lorenzen, I., Price, P.A. Arthritis Rheum. (1999) [Pubmed]
  9. Evaluation of serum biomarkers of fibrosis and injury in Egyptian patients with chronic hepatitis C. Esmat, G., Metwally, M., Zalata, K.R., Gadalla, S., Abdel-Hamid, M., Abouzied, A., Shaheen, A.A., El-Raziky, M., Khatab, H., El-Kafrawy, S., Mikhail, N., Magder, L.S., Afdhal, N.H., Strickland, G.T. J. Hepatol. (2007) [Pubmed]
  10. 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. Rehli, M., Krause, S.W., Andreesen, R. Genomics (1997) [Pubmed]
  11. Functional Variants in the Promoter Region of Chitinase 3-Like 1 (CHI3L1) and Susceptibility to Schizophrenia. Zhao, X., Tang, R., Gao, B., Shi, Y., Zhou, J., Guo, S., Zhang, J., Wang, Y., Tang, W., Meng, J., Li, S., Wang, H., Ma, G., Lin, C., Xiao, Y., Feng, G., Lin, Z., Zhu, S., Xing, Y., Sang, H., St Clair, D., He, L. Am. J. Hum. Genet. (2007) [Pubmed]
  12. gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. Nishikawa, K.C., Millis, A.J. Exp. Cell Res. (2003) [Pubmed]
  13. Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway. Kzhyshkowska, J., Mamidi, S., Gratchev, A., Kremmer, E., Schmuttermaier, C., Krusell, L., Haus, G., Utikal, J., Schledzewski, K., Scholtze, J., Goerdt, S. Blood (2006) [Pubmed]
  14. Isolation and sequence of a novel human chondrocyte protein related to mammalian members of the chitinase protein family. Hu, B., Trinh, K., Figueira, W.F., Price, P.A. J. Biol. Chem. (1996) [Pubmed]
  15. Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. Kirkpatrick, R.B., Emery, J.G., Connor, J.R., Dodds, R., Lysko, P.G., Rosenberg, M. Exp. Cell Res. (1997) [Pubmed]
  16. Changes of biochemical markers of bone turnover and YKL-40 following hormonal treatment for metastatic prostate cancer are related to survival. Johansen, J.S., Brasso, K., Iversen, P., Teisner, B., Garnero, P., Price, P.A., Christensen, I.J. Clin. Cancer Res. (2007) [Pubmed]
  17. Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy. Baeten, D., Kruithof, E., De Rycke, L., Boots, A.M., Mielants, H., Veys, E.M., De Keyser, F. Arthritis Res. Ther. (2005) [Pubmed]
  18. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Volck, B., Price, P.A., Johansen, J.S., Sørensen, O., Benfield, T.L., Nielsen, H.J., Calafat, J., Borregaard, N. Proc. Assoc. Am. Physicians (1998) [Pubmed]
  19. Functional regulatory immune responses against human cartilage glycoprotein-39 in health vs. proinflammatory responses in rheumatoid arthritis. van Bilsen, J.H., van Dongen, H., Lard, L.R., van der Voort, E.I., Elferink, D.G., Bakker, A.M., Miltenburg, A.M., Huizinga, T.W., de Vries, R.R., Toes, R.E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions. Jacques, C., Recklies, A.D., Levy, A., Berenbaum, F. Osteoarthr. Cartil. (2007) [Pubmed]
  21. Regulation of YKL-40 expression during genotoxic or microenvironmental stress in human glioblastoma cells. Junker, N., Johansen, J.S., Hansen, L.T., Lund, E.L., Kristjansen, P.E. Cancer Sci. (2005) [Pubmed]
  22. T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles. Cope, A.P., Patel, S.D., Hall, F., Congia, M., Hubers, H.A., Verheijden, G.F., Boots, A.M., Menon, R., Trucco, M., Rijnders, A.W., Sønderstrup, G. Arthritis Rheum. (1999) [Pubmed]
  23. Enhanced expression of the human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) in osteoarthritic cartilage. Steck, E., Breit, S., Breusch, S.J., Axt, M., Richter, W. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  24. Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. Junker, N., Johansen, J.S., Andersen, C.B., Kristjansen, P.E. Lung Cancer (2005) [Pubmed]
  25. The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha. Ling, H., Recklies, A.D. Biochem. J. (2004) [Pubmed]
  26. YKL-40 is a differential diagnostic marker for histologic subtypes of high-grade gliomas. Nutt, C.L., Betensky, R.A., Brower, M.A., Batchelor, T.T., Louis, D.N., Stemmer-Rachamimov, A.O. Clin. Cancer Res. (2005) [Pubmed]
  27. YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Pelloski, C.E., Mahajan, A., Maor, M., Chang, E.L., Woo, S., Gilbert, M., Colman, H., Yang, H., Ledoux, A., Blair, H., Passe, S., Jenkins, R.B., Aldape, K.D. Clin. Cancer Res. (2005) [Pubmed]
  28. YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization. Nordenbaek, C., Johansen, J.S., Junker, P., Borregaard, N., Sørensen, O., Price, P.A. J. Infect. Dis. (1999) [Pubmed]
  29. Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity. Johansen, J.S., Stoltenberg, M., Hansen, M., Florescu, A., Hørslev-Petersen, K., Lorenzen, I., Price, P.A. Rheumatology (Oxford, England) (1999) [Pubmed]
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