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作 者:陈蕾[1] 刘华[1] 李燕[2] Chen Lei;Liu Hua;Li Yan(Department of Blood Purifying,First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710061,Shaanxi Province,China;Department of Nephrology,First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710061,Shaanxi Province,China)
机构地区:[1]西安交通大学第一附属医院血液净化科,西安710061 [2]西安交通大学第一附属医院肾脏内科,西安710061
出 处:《中华肾病研究电子杂志》2020年第6期241-246,共6页Chinese Journal of Kidney Disease Investigation(Electronic Edition)
基 金:国家自然科学基金(81900675)。
摘 要:目的系膜增殖性肾炎是世界范围内高发的肾小球疾病,其发病与系膜细胞异常增殖有关,但调控系膜细胞增殖的内在分子机制尚不明确。本研究旨在探索TRIM55对大鼠系膜细胞(RMCs)增殖的调控作用及机制。方法向8周龄雄性SD大鼠尾静脉注射2.5 mg/kg抗Thy-1抗体建立抗Thy-1肾炎模型。PAS染色观察肾脏病理表现,qPCR检测大鼠肾小球TRIM55 mRNA表达量;利用质粒及siRNA转染分别得到TRIM55过表达及低表达的RMCs,利用流式细胞仪检测其细胞周期;Western印迹检测p27及Cyclin D1的蛋白表达量。结果TRIM55在抗Thy-1肾炎模型系膜增殖期高表达(P<0.01,T=3.625)。体外RMCs中,TRIM55过表达可促进RMCs细胞周期由G1期向G2/S期转化,诱导系膜细胞增殖(P<0.01,T=13.1);TRIM55低表达可引起RMCs的G1期阻滞,抑制RMCs增殖(P<0.01,T=5.31)。此外,TRIM55过表达可下调p27表达、上调Cyclin D1;反之,TRIM55低表达可上调p27表达、下调Cyclin D1。结论TRIM55可通过调节p27及Cyclin D1表达水平影响细胞由G1期到G2/S期的转化,进而调控RMCs的增殖。Objective Mesangial proliferative nephritis is a glomerular disease with high incidence worldwide.Its pathogenesis is related to the abnormal proliferation of mesangial cells,but the intrinsic molecular mechanism regulating the proliferation of mesangial cells is still unclear.This study aimed to explore the regulation and mechanism of tripartite motif-containing 55(TRIM55)in the proliferation of rat mesangial cells(RMCs).Methods 8-week-old SD rats were injected with 2.5 mg/kg anti-Thy-1 antibody through the tail vein to establish an anti-Thy-1 nephritis model.PAS staining was used for kidney pathology observation,and quantitative polymerase chain reaction(qPCR)used to detect the expression of TRIM55 mRNA in rat glomeruli.TRIM55 plasmid transfection and siRNA transfection were used to obtain over-expression and low-expression of TRIM55 in RMCs,respectively,and the cell cycle was examined by flow cytometry.Western blot was used for detecting the protein expression of p27 and cyclin D1.Results TRIM55 was highly expressed during the mesangial proliferation phase of the anti-Thy-1 nephritis model(P<0.01,T=3.625).In vitro RMCs,TRIM55 overexpression could promote the transformation of RMCs from cell cycle G1 phase to G2/S phase,and induce mesangial cell proliferation(P<0.01,T=13.1).Low expression of TRIM55 could cause block of G1 phase of RMCs and inhibit the proliferation of RMCs(P<0.01,T=5.31).In addition,overexpression of TRIM55 could down-regulate p27 expression and up-regulate cyclin D1 expression.Conversely,low TRIM55 expression could up-regulate p27 expression and down-regulate cyclin D1 expression.Conclusion TRIM55 could affect the transformation of cells from G1 phase to G2/S phase by regulating the expression of p27 and cyclin D1,thereby regulating the proliferation of RMCs.
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