Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice
Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice
复制标题
DOI：
10.1016/j.bbrc.2006.05.084
复制
发表时间：
2006-07-14
影响因子：
3.1
通讯作者：
Shiota, Goshi
中科院分区：
文献类型：
--
作者：
Kanbe, Takamasa;Murai, Rie;Shiota, Goshi
溃疡性结肠炎（UC）是一种进行性和复发性疾病。为探讨肝细胞生长因子（hepatocyte growth factor，HGF）裸基因治疗UC的疗效，采用葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的小鼠结肠炎模型，经直肠给予驱动HGF基因的SR α启动子。在表面上皮中观察到转基因的表达。固有层和粘膜肌层。与对照组小鼠相比，HGF治疗组小鼠结肠粘膜损伤减轻，体重增加（分别为P < 0.01和P < 0.05）。与对照组相比，HGF治疗组小鼠PCNA阳性细胞数增加，凋亡细胞数减少（P < 0.01）。磷酸化AKT显着增加后，HGF基因管理，但磷酸化ERK 1/2没有改变。微阵列分析显示，HGF诱导增殖和凋亡相关基因的表达。这些数据表明，裸HGF基因递送通过调节许多下游基因而引起治疗效果。(c)2006年爱思唯尔公司All rights reserved.
Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SR alpha promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium. lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data Suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes. (c) 2006 Elsevier Inc. All rights reserved.