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首页> 外文期刊>The Biochemical Journal >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 beta-mediated signalling pathways
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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 beta-mediated signalling pathways

机译：几丁质酶3样蛋白人类软骨糖蛋白39（HC-gp39）刺激人类结缔组织细胞增殖，并激活细胞外信号调节激酶和蛋白激酶β介导的信号通路

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Human cartilage glycoprotein 39 (HC-gp39) is a glycoprotein secreted by articular chondrocytes, synoviocytes and macrophages. Increased levels of HC-gp39 have been demonstrated in synovial fluids of patients with rheumatoid or osteoarthritis. The increased secretion of HC-gp39 under physiological and pathological conditions with elevated connective-tissue turnover suggests its involvement in the homoeostasis of these tissues. We report here that HC-gp39 promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts. 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, At suboptimal concentrations, the two growth factors work in a synergistic fashion. The use of selective inhibitors of the mitogen-activated protein kinase and the protein kinase B (AKT) signalling pathways indicates that both are involved in mediating the mitogenic response to HC-gp39. Phosphorylation of both extracellular signal-regulated kinases 1/2 and AKT occurred in a dose- and time-dependent fashion upon addition of HC-gp39. Activation of these signalling pathways could also be demonstrated in human chondrocytes. 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.
机译：人软骨糖蛋白39（HC-gp39）是关节软骨细胞，滑膜细胞和巨噬细胞分泌的糖蛋白。类风湿性关节炎或骨关节炎患者的滑液中已证明HC-gp39水平升高。在生理和病理条件下，伴随结缔组织更新的增加，HC-gp39的分泌增加表明它参与了这些组织的同位转移。我们在这里报告，HC-gp39促进人类滑膜细胞以及皮肤和胎儿肺成纤维细胞的生长。当每个成纤维细胞细胞系暴露于浓度为0.1至2 nM的HC-gp39时，观察到剂量依赖性的生长刺激，这与特征充分的促分裂原，胰岛素样生长因子的有效剂量相似-1，在次优浓度下，两个生长因子以协同方式起作用。使用促分裂原活化蛋白激酶和蛋白激酶B（AKT）信号通路的选择性抑制剂表明两者都参与介导对HC-gp39的促有丝分裂反应。添加HC-gp39后，细胞外信号调节激酶1/2和AKT的磷酸化均呈剂量和时间依赖性。这些信号传导途径的激活也可以在人类软骨细胞中得到证实。因此，HC-gp39在结缔组织细胞中引发信号传导级联反应，从而导致细胞增殖增加，表明该蛋白可能在导致组织纤维化的病理状况中起主要作用。

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