Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells
Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells
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DOI：
10.1152/ajpgi.00511.2005
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发表时间：
2006-04-01
影响因子：
4.5
通讯作者：
Shimosegawa, T
中科院分区：
文献类型：
--
作者：
Masamune, A;Satoh, M;Shimosegawa, T
半乳糖凝集素-1诱导胰腺星状细胞产生趋化因子和增殖。美国生理学胃肠和肝脏生理学杂志290：G729-G736，2006年。首次发表于2005年12月22日; doi：10.1152/ajpgi.00511.2005。半乳糖凝集素-1是一种β-半乳糖苷结合凝集素。先前的研究表明，半乳凝素-1在慢性胰腺炎和与胰腺癌相关的促结缔组织增生反应的成纤维细胞中表达。这些成纤维细胞现在被认为是活化的胰腺星状细胞（PSC）。在这里，我们研究了半乳糖凝集素-1在PSC细胞功能中的作用。PSC从大鼠胰腺组织中分离并以其培养物活化的表型使用，除非另有说明。通过Western印迹分析、RT-PCR和免疫荧光染色评估半乳糖凝集素-1的表达。评价了重组半乳糖凝集素-1对趋化因子产生和增殖的影响。通过EMSA评估转录因子的激活。使用抗磷酸特异性抗体通过Western印迹分析检测MAPK的活化。半乳糖凝集素-1在培养物活化的PSC中强烈表达，但在新鲜分离的PSC中不表达。重组半乳糖凝集素-1增加单核细胞趋化蛋白-1和胡萝卜素诱导的中性粒细胞趋化蛋白-1的增殖和产生。Galectin-1激活ERK、JNK、激活蛋白-1和NF-κ B，但不激活p38 MAPK或Akt。半乳糖凝集素-1通过ERK和趋化因子的产生诱导增殖，主要通过激活NF-κ B，部分通过JNK和ERK途径。半乳糖凝集素-1的这些作用在硫代二乳糖苷（一种β-半乳糖苷结合的抑制剂）的存在下被消除。总之，我们的研究结果表明，半乳糖凝集素-1在趋化因子的生产和增殖中的作用，通过其β-半乳糖苷结合活性在活化的PSC。
Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol 290: G729-G736, 2006. First published December 22, 2005; doi: 10.1152/ajpgi.00511.2005. Galectin-1 is a beta-galactoside-binding lectin. Previous studies have shown that galectin-1 was expressed in fibroblasts of chronic pancreatitis and of desmoplastic reaction associated with pancreatic cancer. These fibroblasts are now recognized as activated pancreatic stellate cells (PSCs). Here, we examined the role of galectin-1 in cell functions of PSCs. PSCs were isolated from rat pancreatic tissue and used in their culture-activated phenotype unless otherwise stated. Expression of galectin-1 was assessed by Western blot analysis, RT-PCR, and immunofluorescent staining. The effects of recombinant galectin-1 on chemokine production and proliferation were evaluated. Activation of transcription factors was assessed by EMSA. Activation of MAPKs was examined by Western blot analysis using antiphosphospecific antibodies. Galectin-1 was strongly expressed in culture-activated but not freshly isolated PSCs. Recombinant galectin-1 increased proliferation and production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1. Galectin-1 activated ERK, JNK, activator protein-1, and NF-kappa B, but not p38 MAPK or Akt. Galectin-1 induced proliferation through ERK and chemokine production mainly through the activation of NF-kappa B and in part by JNK and ERK pathways. These effects of galectin-1 were abolished in the presence of thiodigalactosie, an inhibitor of beta-galactoside binding. In conclusion, our results suggest a role of galectin-1 in chemokine production and proliferation through its beta-galactoside binding activity in activated PSCs.