Action mechanisms of galectin-1, CNTF and phosphacan for the regulation of axonal regeneration

半乳糖凝集素-1、CNTF和磷酸聚糖调节轴突再生的作用机制

基本信息

批准号：
17500267
负责人：
SANGO Kazunori
金额：
$ 2.24万
依托单位：
Tokyo Metropolitan Organization for Medical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500267/
关键词：
axonal regeneration galectin-1 ciliary neurotrophic factor phosphacan neuronal cell culture dorsal root ganglion neurons Schwann cells signal transduction 脊髄後根神経節細胞マクロファージ網膜

项目摘要

We investigated the action mechanisms of growth-promoting molecules such as oxidized galectin-1 and ciliary neurotrophic factor (CNTF) and regulatory molecules such as chondroitin sulfate proteoglycans (especially phosphacan) in axonal regeneration after injury.(1)Galectin-1 and CNTF : Immunohistochemistry on the sections of adult rat dorsal root ganglia (DRG) revealed that galectin-1 was abundantly expressed in small-diameter sensory neurons and Schwann cells while CNTF expression was restricted to Schwann cells. In contrast to the findings in vivo, we observed intense immunoreactivity for both galectin-1 and CNTF in DRG neurons after 3 hours, 2 days and 7 days in culture. At later stages of culture, the immunoreactivity was detected in regenerating neurites. These results suggest that both molecules are synthesized and transported to neurites in cultured DRG neurons. In spite of lacking signal leading sequences, galectin-1 is likely to be externalized from intact DRG neurons and Schw … More ann cells through the non-classical secretory pathway, whereas CNTF appears to be released from disrupted Schwann cells after peripheral nerve injury. Galectin-1 converted from the reduced form to the oxidized form in the extracellular space is likely to stimulate macrophages to secrete several factors (e.g. interleukin-6, bran derived neurotrophic factor), while CNTF directly acts on DRG neurons to activate signal transduction pathways (e.g. JAK-STAT3, MEK-MAPK, PI3K-Akt).(2)Chondroitin sulfate proteoglycans : Phosphacan purified from embryonic (E20) or postnatal (P7, P20) rat brain impaired attachment and neurite outgrowth of cultured adult rat DRG neurons. These inhibitory effects were dependent on dose (10μg/ml>1μg/ml>>0.1μg/ml) and age of rats from which the molecule was purified (P20>P7>E20). Since the structure of chondroitin sulfate of these preparations are immunologically and compositionally different, these findings suggest that variation of chondroitin sulfate chains plays important roles in the regulatory actions of phosphacan. Less

我们研究了氧化半乳糖凝集素1和睫状神经营养因子（CNTF）等生长促进分子和硫酸软骨素蛋白聚糖（特别是磷酸聚糖）等调节分子在损伤后轴突再生中的作用机制。（1）Galectin-1和CNTF：成年大鼠背根神经节 (DRG) 切片的免疫组织化学显示，galectin-1在小直径感觉神经元和雪旺细胞中大量表达，而 CNTF 表达仅限于雪旺细胞。与体内研究结果相反，我们在 3 小时、2 天和培养7天后，在再生神经突中检测到免疫反应性，这些结果表明尽管缺乏信号，这两种分子仍被合成并转运至培养的DRG神经元中。在主导序列中，Galectin-1 很可能通过非经典分泌途径从完整的 DRG 神经元和雪旺细胞中外化，而 CNTF 似乎是在周围神经损伤后从受损的雪旺细胞中释放出来。细胞外空间的氧化形式可能会刺激巨噬细胞分泌多种因子（例如白细胞介素6、麸皮衍生神经营养因子），而CNTF则直接作用于DRG神经元激活信号转导途径（例如 JAK-STAT3、MEK-MAPK、PI3K-Akt）。(2) 硫酸软骨素蛋白聚糖：从胚胎 (E20) 或出生后 (P7、P20) 大鼠大脑受损的附着和神经突生长中纯化的磷酸聚糖培养的成年大鼠 DRG 神经元的这些抑制作用取决于剂量。 (10μg/ml>1μg/ml>>0.1μg/ml)和纯化该分子的大鼠的年龄(P20>P7>E20)由于这些制剂的硫酸软骨素结构在免疫学和成分上不同，所以这些发现。表明硫酸软骨素链的变异在磷酸聚糖的调节作用中发挥重要作用。