移植雄性骨髓的雌性小鼠肝组织肝再生相关基因的信号通路  

Liver regeneration-related gene signaling pathways in female mice transplanted bone marrow from male mice

作　　者：李晶津[1] 李瀚旻[2] 高翔[2] 晏雪生[2] 

机构地区：[1]武汉大学医学院2003级临床医学专业,湖北省武汉市430072 [2]湖北中医学院附属医院肝病研究所,湖北省武汉市430061

出　　处：《世界华人消化杂志》2008年第2期150-155,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金重大研究计划项目;No.90709041~~;国家自然科学基金;No.30672590;30271562;30371787~~;国家重大基础研究973资助项目;No.2002CCC00300~~;湖北省自然科学基金;No.2001ABB171~~

摘　　要：目的:探讨骨髓形成肝细胞的分子机制.方法:采用移植♂骨髓的♀小鼠模型,♀Balb/ c小鼠随机分为模型组和正常对照组,选用小鼠基因表达谱寡核苷酸芯片,利用反转录酶合成掺有荧光标记的cDNA探针,将探针与基因表达谱芯片杂交观察小鼠肝组织基因表达谱的变化,筛选样本之间杂交信号比值有差异表达的基因.采用生物信息学方法分析模型组中小鼠肝组织再生相关基因的信号通路变化规律.结果:♀小鼠在移植♂骨髓6mo后肝组织的基因表达谱显著不同,对照组相对于正常组的差异表达基因有865条,已知功能基因有447条,其中上调基因92条,下调基因355条.与肝再生相关基因信号通路涉及HGF,TGF-β,Focal Adhesion,JAK-Stat,VEGF等信号通路,他们相关基因的上调表达促进肝细胞的增殖分化.TGF-β信号通路中相关基因下调,抑制信号通路的激活,减弱肝再生的负性作用,利于肝细胞的增殖分化.结论:♀小鼠移植♂骨髓后的肝组织基因表达谱显著变化,有可能通过其肝再生相关基因的信号通路激活或抑制调节肝再生.AIM： To probe into the mechanism underlying the transformation of bone marrow into hepatic cells. METHODS： Inter-sexual bone marrow transplantation models were induced by transplanting bone marrow from male mice into the liver cells from female mice. Female Balb/C mice were randomly divided model group and normal control group. The oligo-necleotide acid chip with mouse gene expression spectrum was selected, and reverse transcription enzyme was used to synthesize the fluorescence-labeled cDNA probe. The probe and gene expression microchip were hybridized to observe changes of gene expression in the liver issues, and genes with a different hybrid signal ratio were selected and the changes of liver regeneration-related gene pathways in female mice transplanted bone marrow from male mice were analyzed. RESULTS： A significance difference in the expression of genes was found in liver tissue from the female mice transplanteci bone marrow from male mice after 6 mo between the model and normal control groups. Eight hundred and sixty-five genes had different expressions, including 447 recognized functional genes, of which 92 were up-regulated genes and 355 down-regulated genes. The up-regulated genes involving the signal pathways of HGF, TGF-β, focal adhesion, JAK-Stat and VEGF could promote the proliferation and differentiation of hepatic cells. The down-regulated genes could inhibit the activation of TGF-β signaling pathways and the negative effect of liver regeneration, thus contributing to the proliferation and differentiation of liver cells. CONCLUSION： The gene expression spectrum is remarkably changed in liver tissue from female mice transplanted bone marrow from male mice by activating gene signal pathways and inhibiting liver regeneration.

关 键 词：骨髓移植 肝再生 基因芯片 基因表达谱 信号通路 

分 类 号：R346[医药卫生—基础医学]