Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin
Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin
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DOI：
10.1172/jci119429
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发表时间：
1997-05-15
影响因子：
15.9
通讯作者：
Kanwar, YS
中科院分区：
文献类型：
--
作者：
Wada, J;Ota, K;Kanwar, YS
Galectin-9是一种β-半乳糖苷结合凝集素，最近从小鼠胚胎肾脏中分离出来。本研究对其生物学功能及其在胚胎、新生和成年小鼠组织中的表达进行了研究。Northern杂交分析发现，该基因分布广泛，且表达受发育调控。原位杂交研究显示，Galectin-9在胚胎小鼠的肝脏和胸腺中表达增强。在出生后的小鼠中，包括胸腺上皮细胞在内的各种组织中都观察到了抗Galectin-9的免疫反应。Galectin-9在胸腺中的高表达使我们研究了它在胸腺细胞克隆性删除中的作用。产生的融合蛋白保留了乳糖结合活性，就像内源性Galectin-9一样。用末端脱氧转移酶介导的dUTP缺口末端标记法检测，2.5 mM浓度的Galectin-9可诱导近30%的胸腺细胞发生凋亡。细胞的凋亡作用呈剂量依赖性，乳糖可被抑制。在较高浓度时，可诱导胸腺细胞同型聚集。电子显微镜显示，在Galectin-9存在的情况下，60%的胸腺细胞发生了凋亡。免疫荧光显微镜下，部分胸腺细胞发生凋亡，胞质膜上可见Galectin-9。Galectin-9不能诱导肝细胞凋亡。综上所述，这些发现表明Galectin-9，一种发育调节的凝集素，在胸腺细胞-上皮相互作用中发挥作用，与胸腺生物学有关。
Galectin-9, a beta-galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, and adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed and its expression was developmentally regulated. In situ hybridization studies revealed an accentuated expression of galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. The high expression of galectin-9 in the thymus led us to investigate its role in the clonal deletion of thymocytes. Fusion proteins were generated, which retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at 2.5 mu M concentration, induced apoptosis in similar to 30% of the thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end labeling method. The apoptotic effect was dose dependent and lactose inhibitable. At higher concentrations, it induced homotypic aggregation of the thymocytes. Electron microscopy revealed similar to 60% of the thymocytes undergoing apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9. Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these findings indicate that galectin-9, a developmentally regulated lectin, plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus.