| HMGA2基因调控Notch信号通路对高糖诱导的肾小管上皮细胞凋亡的影响 |
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| 引用本文： | 方晓琳,杨海波,李宪,胡涛,张一诺,孙广平. HMGA2基因调控Notch信号通路对高糖诱导的肾小管上皮细胞凋亡的影响[J]. 中国病理生理杂志, 2019, 0(7): 1261-1267 |
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| 作者姓名： | 方晓琳 杨海波 李宪 胡涛 张一诺 孙广平 |
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| 作者单位： | 吉化集团公司总医院内分泌科;吉化集团公司总医院血液中毒科 |
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| 基金项目： | 吉林市科技创新发展计划项目(No.201536105) |
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| 摘 要： | 目的:探讨下调HMGA2基因表达对高糖(HG)诱导的肾小管上皮细胞凋亡及Notch信号的影响。方法:分别用5、10、20和30 mmol/L的D-葡萄糖刺激人肾小管上皮HK-2细胞2 h及30 mmol/L的D-葡萄糖刺激HK-2细胞10 min、60 min和120 min,通过Western blot检测HMGA2蛋白的表达。将HK-2细胞分为4个处理组,即正常葡萄糖(NG)组、HG组、HG+si-HMGA2组和HG+NC组,其中siRNA转染参照LipofectamineTM 2000说明。处理细胞48 h,流式细胞术检测细胞凋亡率;活性氧簇(ROS)检测试剂盒测定细胞ROS含量;Western blot检测Notch1、Hes1、Bcl-2和Bax的蛋白表达。使用Notch信号通路抑制剂DAPT处理HK-2细胞,将细胞分为HG组、HG+DAPT组和HG+si-HMGA2+DAPT组,通过流式细胞术检测细胞凋亡率。结果:不同浓度D-葡萄糖处理HK-2细胞及D-葡萄糖处理HK-2细胞不同时间均可明显上调HMGA2蛋白的表达,与5 mmol/L D-葡萄糖或0 min比较差异均具有统计学意义(P<0.05)。与NG组比较,HG组HMGA2、Notch1和Hes1蛋白的表达明显升高,Bcl-2/Bax表达明显降低,细胞凋亡率明显升高,ROS含量明显升高(P<0.05);和HG组比较,HG+si-HMGA2组HMGA2、Notch1和Hes1蛋白表达明显降低,Bcl-2/Bax表达明显升高,细胞凋亡率降低,ROS含量明显降低(P<0.05)。HG+DAPT组的细胞凋亡率明显低于HG组,而HG+si-HMGA2+DAPT组的细胞凋亡率明显低于HG+DAPT组(P<0.05)。结论:下调HMGA2基因表达可通过调控Notch信号通路、降低细胞内ROS产生而抑制肾小管上皮细胞凋亡。
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| 关 键 词： | HMGA2基因 糖尿病肾病 肾小管上皮细胞 细胞凋亡 NOTCH信号通路 |
Effect of HMGA2 gene on high glucose-induced apoptosis of renal tubular epithelial cells by regulating Notch signaling pathway |
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| FANG Xiao-lin,YANG Hai-bo,LI Xian,HU Tao,ZHANG Yi-nuo,SUN Guang-ping. Effect of HMGA2 gene on high glucose-induced apoptosis of renal tubular epithelial cells by regulating Notch signaling pathway[J]. Chinese Journal of Pathophysiology, 2019, 0(7): 1261-1267 |
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| Authors: | FANG Xiao-lin YANG Hai-bo LI Xian HU Tao ZHANG Yi-nuo SUN Guang-ping |
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| Affiliation: | (Department of Endocrinology, Jihua Group General Hospital, Jilin 132021, China;Department of Blood Poisoning, Jihua Group General Hospital, Jilin 132021, China) |
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| Abstract: | AIM: To investigate the effect of HMGA2 down-regulation on apoptosis and Notch signaling pathway in renal tubular epithelial cells exposed to high glucose(HG). METHODS: D-glucose at 5, 10, 20 and 30 mmol/L was used to stimulate human renal tubular epithelial HK-2 cells for 2 h, and D-glucose at 30 mmol/L was used to stimulate the HK-2 cells for 10 min, 60 min and 120 min. The protein expression of HMGA2 was determined by Western blot. The HK-2 cells were divided into normal glucose(NG) group, HG group, HG+si-HMGA2 group and HG+NC group, in which siRNA was transfected by LipofectamineTM 2000 for 48 h. Flow cytometry was used to analyze the apoptotic rate, reactive oxygen species(ROS) assay kit was used to detect ROS content, and Western blot was used to detect the protein levels of Notch1, Hes1 and Bcl-2. The HK-2 cells were treated with the Notch signaling pathway inhibitor DAPT, and then the cells were divided into HG group, HG+DAPT group and HG+si-HMGA2+DAPT group. The apoptotic rate was analyzed by flow cytometry. RESULTS: Exposure of the HK-2 cells to D-glucose at different concentrations for different time significantly increased the expression of HMGA2(P<0.05). Compared with NG group, the protein expression of HMGA2, Notch1 and Hes1 in HG group was increased, the expression of Bcl-2/Bax was decreased, the apoptotic rate was increased, and the content of ROS was increased obviously(P<0.05). Compared with HG group, the protein expression of HMGA2, Notch1 and Hes1 of HG+si-HMGA2 group was decreased, the expression of Bcl-2/Bax was increased, the apoptotic rate was decreased, and the content of ROS was decreased significantly(P<0.05). The apoptotic rate in HG+DAPT group was significantly lower than that in HG group, while the apoptotic rate in HG+si-HMGA2+DAPT group was significantly lower than that in HG+DAPT group(P<0.05). CONCLUSION: Down-regulation of HMGA2 expression inhibits the apoptosis of renal tubular epithelial cells by regulating Notch signaling pathway and decreasing ROS production. |
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| Keywords: | HMGA2 gene Diabetic nephropathy Renal tubular epithelial cells Apoptosis Notch signaling pathway |
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