High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina.
High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina.
复制标题
DOI：
10.1155/2013/863036
复制
发表时间：
2013
影响因子：
4.6
通讯作者：
Mohammad G
中科院分区：
文献类型：
--
作者：
Abu El-Asrar AM;Nawaz MI;Siddiquei MM;Al-Kharashi AS;Kangave D;Mohammad G
为了验证脑源性神经营养因子-(BDNF-)介导的神经保护作用被糖尿病视网膜中的高迁移率组盒-1 （HMGB1）降低的假设，我们对46例增生性糖尿病视网膜病变患者和34例非糖尿病患者的配对玻璃体和血清样本进行了BDNF、HMGB1、晚期糖基化终产物可溶性受体（sRAGE）、可溶性细胞间粘附分子-1 （sICAM-1）、单核细胞化学引诱蛋白-1 （MCP-1）和TBARS的检测。我们还检查了糖尿病大鼠和HMGB1玻璃体内注射大鼠的视网膜。研究HMGB1抑制剂甘草酸对糖尿病视网膜BDNF表达变化的影响。采用Western blot、ELISA和TBARS检测。玻璃体样品中未检测到BDNF。与非糖尿病患者相比，糖尿病患者血清样本中的BDNF水平显著降低，而糖尿病患者血清样本中的HMGB1、sRAGE、sICAM-1和TBARS水平显著升高。MCP-1水平无显著性差异。血清BDNF水平与HMGB1呈显著负相关。糖尿病和玻璃体内给予HMGB1诱导大鼠视网膜中HMGB1、TBARS和cleaved caspase-3的表达显著上调，而BDNF和synaptophysin的表达显著下调。甘草酸显著减弱糖尿病诱导的BDNF下调。本研究提示hmgb1诱导的BDNF下调可能参与了糖尿病视网膜神经变性的发病机制。
To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.
登录
查看更多内容
影响因子：
--
作者：
Mollica, Luca;De Marchis, Francesco;Bianchi, Marco E.
通讯作者：
Bianchi, Marco E.
影响因子：
2.8
作者：
Luan, Zheng-Gang;Zhang, Hao;Guo, Ren-Xuan
通讯作者：
Guo, Ren-Xuan
影响因子：
4.4
作者：
Dvoriantchikova, Galina;Hernandez, Eleut;Ivanov, Dmitry
通讯作者：
Ivanov, Dmitry
影响因子：
4.4
作者：
Kaji, Yuichi;Usui, Tomohiko;Adamis, Anthony P.
通讯作者：
Adamis, Anthony P.
影响因子：
5.3
作者：
Kim, Jung-Bin;Choi, Joon Sig;Lee, Ja-Kyeong
通讯作者：
Lee, Ja-Kyeong