目的探讨溃疡性结肠炎(ulcerative colitis,UC)患者肠道机械屏障变化与信号转导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)信号通路的关系。方法收集200例UC患者肠黏膜组织作为UC组,以50名健康体检者...目的探讨溃疡性结肠炎(ulcerative colitis,UC)患者肠道机械屏障变化与信号转导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)信号通路的关系。方法收集200例UC患者肠黏膜组织作为UC组,以50名健康体检者肠黏膜标本为对照组。UC患者以Mayo评分分为轻度(68例)、中度(70例)和重度(62例)。免疫组化法检测咬合蛋白(Occludin)、紧密连接蛋白l(Claudin-1)和STAT3蛋白表达,并对相关临床指标进行统计学分析。结果与对照组相比,UC组Occludin、Claudin-1的表达水平显著降低(P<0.05),STAT3表达水平明显升高(P<0.05)。三种蛋白的表达水平在轻、中、重度UC组间相比,差异均有统计学意义(P<0.05),其中Occludin和Claudin-1表达随着UC分级增加显著减少(rs=-0.914,rs=-0.933,P<0.05),STAT3表达随着UC分级增加而显著增多(rs=0.942,P<0.05)。Occludin及Claudin-1表达水平与STAT3表达水平呈负相关(r=-0.924,r=-0.983,P<0.05)。结论 STAT3信号通路可能通过影响肠黏膜上皮细胞间紧密连接蛋白Occludin和Claudin-1的表达引起UC肠黏膜机械屏障损伤。STAT3基因可能成为干预治疗UC的一个潜在靶点。展开更多
上皮组织细胞必须极化其表面区域以执行其转运生理功能。不同膜转运蛋白定位于细胞膜的不同区域,而细胞与细胞之间则须通过紧密连接复合体紧密连接成极化区域,并调节旁细胞途径的通透性。精密的机体要求上皮细胞具备一个筛选装置,用于...上皮组织细胞必须极化其表面区域以执行其转运生理功能。不同膜转运蛋白定位于细胞膜的不同区域,而细胞与细胞之间则须通过紧密连接复合体紧密连接成极化区域,并调节旁细胞途径的通透性。精密的机体要求上皮细胞具备一个筛选装置,用于将新合成的转运蛋白定位于合适的表面区域;转运蛋白本身也必须内含规定其功能位置的分选信号。目前上皮细胞蛋白分选和蛋白质之间相互作用已被逐渐阐明。上皮细胞通过细胞信号转导途径形成极化初始状态,将自己定位于特定位置,调节细胞与细胞之间、细胞与基质之间的相互作用。最近研究发现其信号转导通路的一个成员是一种AMP激活的蛋白激酶(AMP-stimulated protein kinase,AMPK),它也是细胞能量感受器。展开更多
Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord ...Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.展开更多
文摘目的探讨溃疡性结肠炎(ulcerative colitis,UC)患者肠道机械屏障变化与信号转导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)信号通路的关系。方法收集200例UC患者肠黏膜组织作为UC组,以50名健康体检者肠黏膜标本为对照组。UC患者以Mayo评分分为轻度(68例)、中度(70例)和重度(62例)。免疫组化法检测咬合蛋白(Occludin)、紧密连接蛋白l(Claudin-1)和STAT3蛋白表达,并对相关临床指标进行统计学分析。结果与对照组相比,UC组Occludin、Claudin-1的表达水平显著降低(P<0.05),STAT3表达水平明显升高(P<0.05)。三种蛋白的表达水平在轻、中、重度UC组间相比,差异均有统计学意义(P<0.05),其中Occludin和Claudin-1表达随着UC分级增加显著减少(rs=-0.914,rs=-0.933,P<0.05),STAT3表达随着UC分级增加而显著增多(rs=0.942,P<0.05)。Occludin及Claudin-1表达水平与STAT3表达水平呈负相关(r=-0.924,r=-0.983,P<0.05)。结论 STAT3信号通路可能通过影响肠黏膜上皮细胞间紧密连接蛋白Occludin和Claudin-1的表达引起UC肠黏膜机械屏障损伤。STAT3基因可能成为干预治疗UC的一个潜在靶点。
基金This work was supported by the National Institute of Health(No.DK17433,DK072614).
文摘上皮组织细胞必须极化其表面区域以执行其转运生理功能。不同膜转运蛋白定位于细胞膜的不同区域,而细胞与细胞之间则须通过紧密连接复合体紧密连接成极化区域,并调节旁细胞途径的通透性。精密的机体要求上皮细胞具备一个筛选装置,用于将新合成的转运蛋白定位于合适的表面区域;转运蛋白本身也必须内含规定其功能位置的分选信号。目前上皮细胞蛋白分选和蛋白质之间相互作用已被逐渐阐明。上皮细胞通过细胞信号转导途径形成极化初始状态,将自己定位于特定位置,调节细胞与细胞之间、细胞与基质之间的相互作用。最近研究发现其信号转导通路的一个成员是一种AMP激活的蛋白激酶(AMP-stimulated protein kinase,AMPK),它也是细胞能量感受器。
基金supported by the State Key Program of National Natural Science Foundation of China,No.81330042(to SQF)the International Cooperation Program of the National Natural Science Foundation of China,No.81620108018(to SQF)
文摘Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.
