Chitinase 3-like protein 2 (CHI3L2, YKL-39) activates phosphorylation of extracellular signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells

Abstract

Human cartilage chitinase 3-like protein 2 (CHI3L2, YKL-39) is secreted by articular chondrocytes, also synoviocytes, lung, and heart. Increased levels of YKL-39 have been demonstrated in synovial fluids of patients with rheumatoid or osteoarthritis as well as in some other pathologies and in malignant tumors, particularly in glioblastomas. It belongs to glycosyl hydrolase family 18 and the most closely related to human cartilage glycoprotein 39 (HC gp-39 or chitinase 3-like protein 1, CHI3L1 or YKL-40), which as it was shown previously, promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts. Dose-dependent growth stimulation was observed when the fibroblastic cell line was exposed to YKL-40 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. The use of selective inhibitors of the mitogen-activated protein kinase (MAP kinase) signaling pathway indicates that both, YKL-40 and IGF-I are involved in phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2). Thus YKL-40 initiates a signaling cascade which leads to increased cell proliferation, suggesting that this protein could play some role in the inhibition of apoptosis. We report here that YKL-39, which as YKL-40 has significantly increased expression in glioblastomas, also activates signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells.