OBJECTIVE AND DESIGN This study investigates the regulatory role of connective tissue growth factor (CTGF) on production of fractalkine, monocyte-chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES) in human mesangial cells, and explore the mechanisms of CTGF action. METHODS Cultured human mesangial cells were treated with CTGF. Expressions of mRNA and proteins of fractalkine, MCP-1 and RANTES were analyzed by real-time polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay, respectively. Expressions of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), phosphoinositide 3-kinase (PI3-K) and protein kinase B (PKB) were assessed by Western blotting. Activities of nuclear factor-KB (NF-KB) were determined by NF-kappaB luciferase reporter assay. RESULTS CTGF enhanced the mRNA expressions and protein release of fractalkine, MCP-1 and RANTES, and the expressions of phosphorylated ERK1/2, PI3-K and PKB, and activities of NF-KB. Blockade of ERK1/2 inhibited the CTGF-induced expression ofphosphorylated ERK1/2 and NF-kappaB, and partially decreased the expressions of the above chemokines. PI3-K blockade downregulated the CTGF-stimulated expressions of phosphorylated PI3-K, PKB and NF-kappaB but not phosphorylated ERK1/2, partially decreased the expressions of the above chemokines. NF-kappaB blockade abrogated the CTGF-activated NF-kappaB and partially decreased the expressions of the above chemokines. Soluble heparin and K252a, an inhibitor of Trk, blocked CTGF-induced production of the above chemokines and the activation of the above signaling proteins. CONCLUSION These results demonstrated that CTGF induces production of fractalkine, MCP-1 and RANTES via ERK1/2 and PI3-K/PKB/NF-kappaB-dependent signal pathway mediated by cell surface heparin sulfate proteoglycans and the tyrosine kinase receptor TrkA in human mesangial cells.

中文翻译：

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信号转导参与CTGF诱导的肾小球系膜细胞趋化因子的产生。

目的和设计本研究调查结缔组织生长因子（CTGF）对人肾小球系膜中fractalkine，单核细胞趋化蛋白-1（MCP-1）的产生以及激活，正常T细胞表达和分泌（RANTES）的调节作用。细胞，并探索CTGF作用的机制。方法用CTGF处理人肾小球系膜细胞。分别通过实时聚合酶链反应（PCR）和酶联免疫吸附法分析了fractalkine，MCP-1和RANTES的mRNA和蛋白质的表达。通过蛋白质印迹评估磷酸化的细胞外信号调节激酶1/2（ERK1 / 2），磷酸肌醇3-激酶（PI3-K）和蛋白激酶B（PKB）的表达。核因子-KB（NF-KB）的活性通过NF-κB荧光素酶报告基因测定。结果CTGF增强了fractalkine，MCP-1和RANTES的mRNA表达和蛋白释放，磷酸化ERK1 / 2，PI3-K和PKB的表达以及NF-KB的活性。阻断ERK1 / 2可抑制CTGF诱导的磷酸化ERK1 / 2和NF-κB的表达，并部分降低上述趋化因子的表达。PI3-K阻断下调了CTGF刺激的磷酸化PI3-K，PKB和NF-κB的表达，但未磷酸化ERK1 / 2，部分降低了上述趋化因子的表达。NF-κB阻滞消除了CTGF激活的NF-κB，部分降低了上述趋化因子的表达。可溶性肝素和Trk抑制剂K252a阻断CTGF诱导的上述趋化因子的产生和上述信号蛋白的活化。