MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington＇s disease mouse models and patients is decreased. However, the effects of microRNA-124 on th...MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington＇s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington＇s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Hunting- ton＇s disease transgenic mouse in the rotarod test. 5-Bromo-2＇-deoxyuridine （BrdU） staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was de- creased. These findings suggest that microRNA-124 slows down the progression of Huntington＇s disease possibly through its important role in neuronal differentiation and survival.展开更多
血管形成是胚胎发育期间的最早进程之一,其对胚胎的正常生长发育非常重要。血管形成和发育进程受一系列基因、转录因子、信号通路等调控。转录因子SOX7(SRY related high mobility group box 7)在调控心血管系统的发育、内皮细胞向造血...血管形成是胚胎发育期间的最早进程之一,其对胚胎的正常生长发育非常重要。血管形成和发育进程受一系列基因、转录因子、信号通路等调控。转录因子SOX7(SRY related high mobility group box 7)在调控心血管系统的发育、内皮细胞向造血细胞转化、动静脉分化等进程中发挥重要作用。其特异性高水平地表达于胚胎的心血管组织,提示其参与调控心血管的形成与发育。SOX7与众多参与调控血管内皮细胞的转录因子存在调节关系,其可通过抑制RUNX1的转录活性,抑制内皮细胞向造血细胞转化。Notch信号通路是调控血管发育和动静脉血管分化的关键通路,SOX7很可能作用于Notch信号通路上游,参与调控动脉和静脉血管的分化。但其调控血管发育的确切分子机制未来需进一步研究。展开更多
目的:研究沉默大鼠肾组织中通用控制核苷酸合成5(general control nonderepressible 5,GCN5)基因、性别决定区Y框蛋白9(SRY related HMG box-9,SOX9)基因对Thy-1肾炎(Thy-1 nephritis,Thy-1N)大鼠肾组织内转化生长因子-β1(transforming...目的:研究沉默大鼠肾组织中通用控制核苷酸合成5(general control nonderepressible 5,GCN5)基因、性别决定区Y框蛋白9(SRY related HMG box-9,SOX9)基因对Thy-1肾炎(Thy-1 nephritis,Thy-1N)大鼠肾组织内转化生长因子-β1(transforming growth factor-β1,TGF-β1)生成的影响。方法:分别用慢病毒(lentivirus,LV)包装GCN5和SOX9发夹状小干扰RNA(shRNA),即制备LV-shGCN5和LV-shSOX9重组病毒。然后行大鼠肾动脉灌注术将LV-shGCN5和LV-shSOX9分别导入大鼠肾脏,再经尾静脉注射兔抗大鼠胸腺细胞抗血清(anti-thymocyte serum,ATS)复制Thy-1N模型。在注射ATS后3 h,取大鼠肾组织,用RTPCR和Western blot检查各组大鼠肾组织中GCN5和SOX9的mRNA及蛋白表达水平,以验证干扰效果及GCN5、SOX9对TGF-β1产生的影响。结果:利用肾动脉灌注术将LV-shGCN5或LV-shSOX9重组病毒导入大鼠肾组织后,不仅能有效沉默相应的靶基因,而且还能下调TGF-β1的表达。结论:沉默大鼠肾组织中GCN5或SOX9基因后能显著抑制Thy-1N大鼠肾内TGF-β1的生成。展开更多
基金supported by a grant(A121911 and HI14C2348)of the Korean Health Technology R&D Project,Ministry of Health&WelfareNational Research Foundation of Korea(NRF)(2011-0012728 and 2014R1A2A1A11051520)
文摘MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington＇s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington＇s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Hunting- ton＇s disease transgenic mouse in the rotarod test. 5-Bromo-2＇-deoxyuridine （BrdU） staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was de- creased. These findings suggest that microRNA-124 slows down the progression of Huntington＇s disease possibly through its important role in neuronal differentiation and survival.
文摘血管形成是胚胎发育期间的最早进程之一,其对胚胎的正常生长发育非常重要。血管形成和发育进程受一系列基因、转录因子、信号通路等调控。转录因子SOX7(SRY related high mobility group box 7)在调控心血管系统的发育、内皮细胞向造血细胞转化、动静脉分化等进程中发挥重要作用。其特异性高水平地表达于胚胎的心血管组织,提示其参与调控心血管的形成与发育。SOX7与众多参与调控血管内皮细胞的转录因子存在调节关系,其可通过抑制RUNX1的转录活性,抑制内皮细胞向造血细胞转化。Notch信号通路是调控血管发育和动静脉血管分化的关键通路,SOX7很可能作用于Notch信号通路上游,参与调控动脉和静脉血管的分化。但其调控血管发育的确切分子机制未来需进一步研究。
