首页|CLEC14A在阿霉素诱导FSGS小鼠模型中对足细胞损伤的保护机制

CLEC14A在阿霉素诱导FSGS小鼠模型中对足细胞损伤的保护机制

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目的 探究CLEC14A在阿霉素诱导局灶节段性肾小球硬化(FSGS)小鼠模型中对足细胞损伤的保护作用,并通过半胱氨酸蛋白酶-3(Caspase-3)、B淋巴细胞癌-2相关蛋白(Bax)和B淋巴细胞瘤-2(Bcl-2)信号通路探讨其机制.方法 将30只C57BL/6小鼠随机分成Sham 组(n=10)、Model 组(n=10)和 CLEC14A siRNA 组(siRNA 组,n=10).将小鼠足细胞MPC5分为对照组、FSGS组、FSGS-siCLEC14A组.采用定量聚合酶链反应(qPCR)检测小鼠肾脏中CLEC14A mRNA及血管内皮生长因子(VEGF)mRNA的水平.采用酶联免疫吸附试验(ELISA)检测小鼠肾脏组织中Caspase-3、Bax和Bcl-1水平.结果 FSGS组及FSGS-siCLEC14A组各时间点的细胞增殖能力低于对照组,差异均有统计学意义(均P<0.05).FSGS-siCLEC14A组的48 h及72 h细胞增殖能力均低于FSGS组,差异均有统计学意义(均P<0.05).与对照组比较,FSGS组和FSGS-siCLEC14A组的细胞凋亡率、Caspase-3、Bax水平上升,而Bcl-2水平下降,差异均有统计学意义(均P<0.05);与FSGS组比较,FSGS-siCLEC14A组的Caspase-3、Bax水平增加,而Bcl-2水平下降,差异均有统计学意义(均P<0.05).与对照组比较,FSGS组和FSGS-siCLEC14A组的24 h尿蛋白定量(24 h UTP)、血肌酐(Scr)及血尿素氮(BUN)水平增加,差异均有统计学意义(均P<0.05);与FSGS组比较,FSGS-siCLEC14A组的24 h UTP、Scr及BUN水平增加,差异均有统计学意义(均P<0.05).与Sham组比较,Model组和siRNA组小鼠的CLEC14A mRNA水平下降,VEGF mRNA上升,差异均有统计学意义(均P<0.05);与Model组比较,siRNA组小鼠的CLEC14A mRNA水平下降,VEGF mRNA上升,差异均有统计学意义(均P<0.05).与Sham组比较,Model组和siRNA组小鼠肾脏中的Caspase-3、Bax水平上升,而Bcl-2水平下降,差异均有统计学意义(均P<0.05);与Model组比较,siRNA组小鼠肾脏中的Caspase-3、Bax水平升高,而Bcl-2水平下降,差异均有统计学意义(均P<0.05).结论 CLEC14A可通过抑制Caspase-3、Bax、Bcl-2信号通路起到保护FSGS小鼠足细胞的作用.
Study on the protective mechanism of CLEC14A against podocyte injury in adriamycin-induced FSGS mouse model
Objective To investigate the protective effect of CLEC14A adriamycin-induced fo-cal segmental glomerulosclerosis(FSGS)on podocyte injury in mice and explore its mechanism from the Caspase-3,Bax and Bcl-2 signal pathway.Methods Thirty C57BL/6 mice were randomly divided into sham group(n=10),Model group(n=10),and CLEC14A siRNA group(siRNA group,n=10).Mouse podocytes MPC5 were divided into control group,FSGS group and FSGS-siCLEC14A group.Quantitative polymerase chain reaction(qPCR)was used to detect CLEC14A mRNA and vas-cularendothelial growth factor(VEGF)mRNA levels in mouse kidneys.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect Caspase-3,Bax and Bcl-2 levels in mouse kidney tissues.Re-sults The cell proliferation capacity of FSGS group and FSGS-siCLEC14A group was lower than that of Sham group at all time points,and the differences were statistically significant(all P<0.05).The cell proliferation ability of FSGS-siCLEC14A group at 48 h and 72 h was lower than that of FSGS group,and the differences were statistically significant(all P<0.05).Compared with control group,apoptosis rate,Caspase-3 and Bax levels in FSGS group and FSGS-siCLEC14A group were significantly increased,while Bcl-2 levels were decreased,with statistical significance(all P<0.05).Compared with FSGS group,Caspase-3 and Bax levels in FSGS-siCLEC14A group were increased,while Bcl-2 levels were decreased,with statistical significance(all P<0.05).Compared with control group,24-hour urinary protein(24 h UTP),serum creatinine(Scr)and blood urea nitrogen(BUN)levels in FSGS group and FSGS-siCLEC14A group were increased,and the differences were statistically signifi-cant(all P<0.05).Compared with FSGS group,24 h UTP,Scr and BUN levels in FSGS-si-CLEC14A group were increased,and the differences were statistically significant(all P<0.05).Compared with Sham group,CLEC14A mRNA level in Model group and siRNA group decreased,VEGF mRNA level increased,and the differences were statistically significant(all P<0.05).Com-pared with Model group,CLEC14A mRNA level in siRNA group decreased,VEGF mRNA level in-creased,and the differences were statistically significant(all P<0.05).Compared with Sham group,the levels of Caspase-3 and Bax in the kidney of mice in Model group and siRNA group were in-creased,while the levels of Bcl-2 were decreased,with statistical significance(all P<0.05).Com-pared with Model group,the levels of Caspase-3 and Bax in kidney of siRNA group were increased,while the levels of Bcl-2 were decreased,with statistical significance(all P<0.05).Conclusions CLEC14A can protect FSGS mouse podocytes through the Caspase-3,Bax and Bcl-2 signal pathway.

Glomerulosclerosis,Focal SegmentalAdriamycinCLEC14APodocytes

刘颖、曹冰、任荣

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新疆医科大学第五附属医院肾病科,乌鲁木齐 830011

肾小球硬化症,局灶节段性 阿霉素 CLEC14A 足细胞

2024

国际泌尿系统杂志
中华医学会,湖南省医学会

国际泌尿系统杂志

CSTPCD
影响因子:0.414
ISSN:1673-4416
年,卷(期):2024.44(3)
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