Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration.
Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration.
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SBMA模型小鼠肝细胞生长因子的过度表达对去势联合治疗具有累加效应。
DOI：
10.1016/j.bbrc.2015.11.015
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Sobue G
中科院分区：
文献类型：
--
作者：
Ding Y;Adachi H;Katsuno M;Huang Z;Jiang YM;Kondo N;Iida M;Tohnai G;Nakatsuji H;Funakoshi H;Nakamura T;Sobue G
脊髓延髓肌萎缩症（Spinal and bulbar muscular atrophy，SBMA）是一种遗传性运动神经元疾病，由雄激素受体（androgen receptor，AR）基因内的多聚谷氨酰胺（polyQ）编码区扩张引起。SBMA的病理特征是脊髓和脑干中的运动神经元丢失以及残留运动神经元和某些内脏器官中的突变AR的弥漫性核积聚和核包涵体。肝细胞生长因子（HGF）是一种具有神经保护作用的多肽生长因子。为了研究HGF过表达是否会影响SBMA小鼠模型的疾病进展，我们将表达AR基因的SBMA转基因小鼠与过表达HGF的小鼠杂交。在这里，我们报告说，高表达的HGF诱导Akt磷酸化和适度改善运动症状的SBMA转基因小鼠模型治疗或去势。这些发现表明，HGF过表达可以提供一个潜在的治疗途径，作为SBMA的疾病修饰疗法的联合治疗。
Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within theandrogen receptor(AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing anARgene with an expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease-modifying therapies in SBMA.