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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（尤其是磷酸蛋白聚糖）等调节分子在损伤后轴突再生中的作用机制。（1）Galectin-1和CNTF：在成年大鼠背根神经节（DRG）切片上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仅在雪旺细胞中表达。与体内研究结果相反，我们观察到在培养3小时、2天和7天后DRG神经元中半乳糖凝集素-1和CNTF的强烈免疫反应性。在培养的后期，在再生的神经突中检测到免疫反应性。这些结果表明，这两种分子的合成和运输到培养的DRG神经元的突起。尽管缺乏信号引导序列，但galectin-1可能从完整的DRG神经元和Schw ...更多信息 ann细胞通过非经典的分泌途径，而CNTF似乎是从周围神经损伤后破坏的雪旺细胞释放。Galectin-1在细胞外空间由还原形式转化为氧化形式，可能刺激巨噬细胞分泌几种因子（例如白细胞介素-6、麸源性神经营养因子），而CNTF直接作用于DRG神经元以激活信号转导通路（例如JAK-STAT 3、MEK-MAPK、PI 3 K-Akt）。（2）硫酸软骨素蛋白聚糖：从胚胎（E20）或出生后（P7，P20）大鼠脑中纯化的Phosphacan损害培养的成年大鼠DRG神经元的附着和轴突生长。这些抑制作用依赖于剂量（10μg/ml>1μg/ml>>0.1μg/ml）和纯化分子的大鼠的年龄（P20>P7>E20）。由于这些制剂的硫酸软骨素的结构在免疫学上和组成上不同，这些发现表明硫酸软骨素链的变化在磷酸蛋白聚糖的调节作用中起重要作用。少

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chondroitin sulfate proteoglycans in the peripheral nervous system after injury.

损伤后周围神经系统中的硫酸软骨素蛋白多糖。

DOI：
发表时间：
期刊：
Neural Proteoglycans (Maeda, N., ed.)(Research Signpost Kerala, India) (in press)
影响因子：
0
作者：
Sango;K.
通讯作者：
K.

Neural Proteoglycans

神经蛋白多糖

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Masu M.;et. al.
通讯作者：
et. al.

An approach to the pathogenesis of diabetic neuropathy with cultured adult animal neurons and Schwann cells. (Japanese)

利用培养的成年动物神经元和施万细胞研究糖尿病神经病变的发病机制。

DOI：
发表时间：
2006
期刊：
Peripheral Nerve (Massho Shinkei) 17
影响因子：
0
作者：
Sango;K.;Saito;H.;Horie;H.
通讯作者：
H.

Medicines for diabetic complications.(Japanese)

治疗糖尿病并发症的药物。（日语）

DOI：
发表时间：
2005
期刊：
Prospects of New Medicines (Shinyaku Tenbo) 41(S-1)
影响因子：
0
作者：
Sango;K.
通讯作者：
K.

Establishment of immortalized Schwann cells from a Sandhoff mouse and corrective effect of recombinant human β- hexosaminidase A on the accumulated GM2 ganglioside

Sandhoff小鼠永生雪旺细胞的建立及重组人β-氨基己糖苷酶A对GM2神经节苷脂积累的纠正作用

DOI：
发表时间：
2005
期刊：
Journal of Human Genetics 50
影响因子：
0
作者：
Ohsawa;M.;Kotani;M.;Tajima;Y.;Tsuji;D.;Ishibashi;Y.;Kuroki;A.;Itoh;K.;Watabe;K.;Sango;K.;Yamanaka;Y.;Sakuraba;H.
通讯作者：
H.