多囊蛋白1氨基端肽对常染色体显性多囊肾囊肿衬里上皮细胞增殖和凋亡的影响

赵海丹;孙田美;王文靖;梅长林;徐成钢;戴兵;沈学飞;张树忠;李林

中华肾脏病杂志 ›› 2005, Vol. 21 ›› Issue (11) : 664-668.
遗传性肾病专题

多囊蛋白1氨基端肽对常染色体显性多囊肾囊肿衬里上皮细胞增殖和凋亡的影响

  • 赵海丹;孙田美;王文靖;梅长林;徐成钢;戴兵;沈学飞;张树忠;李林
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Evaluation of polycystin-1 N-terminal peptide on the proliferation and apoptosis of cystic-lining epithelial cells in human ADPKD

  • ZHAO Hai-dan;SUN Tian-mei ;WANG Wen-jing;MEI Chang-lin;XU Cheng-gang; DAI Bing;SHEN Xue-fei;ZHANG Shu-zhong;LI Lin
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摘要

目的 探讨多囊蛋白1氨基端肽(PC-1NTP)对常染色体显性多囊肾病(ADPKD)肾囊肿衬里上皮细胞增殖、细胞周期和凋亡的影响&#65377;方法 用噻唑蓝(MTT)法检测PC-1NTP对ADPKD囊肿衬里上皮细胞增殖的影响&#65377;用流式细胞仪分析细胞周期与凋亡状况&#65377;用荧光定量PCR检测细胞中细胞周期素cyclinD1、p21WAF1、 bax、bcl-2 和小染色体维护蛋白2(MCM-2)的mRNA表达&#65377;结果 PC-1NTP使ADPKD囊肿衬里上皮细胞G0/G1期细胞百分比显著增多,S期细胞百分比显著减少,并明显抑制其增殖和凋亡;同时细胞中p21和bcl-2 mRNA表达明显增高(P < 0.01),cyclinD1、bax 和MCM-2的mRNA表达明显减弱(P < 0.01或P < 0.05)&#65377;结论 PC-1NTP能明显抑制ADPKD囊肿衬里上皮细胞的增殖和凋亡,减慢细胞周期进程,其作用机制可能是通过调节G1/S关卡调节因子cyclinD1/p21WAF1和凋亡调节蛋白bcl-2/bax的表达实现的&#65377;PC-1NTP有希望成为治疗ADPKD的可选药物&#65377;

Abstract

Objective To investigate the effects of polycystin-1 N-terminal peptide (PC-1NTP) on proliferation, cell cycle and apoptosis of cystic-lining epithelial cells in human autosomal dominant polycystic kidney disease (ADPKD). Methods Cystic-lining epithelial cells were treated with PC-1NTP in vitro. MTT assay was used to detect the PC-1NTP effects on cells proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The mRNA expression of cyclinD1, p21WAF1, bax, bcl-2 and MCM-2 were measured by fluorescence quantitative PCR. Results The growth and apoptosis of cystic-lining epithelial cells were significantly inhibited by PC-1NTP. The percentage of cells in G0/G1 phase increased, while decreased in S phase remarkably. The mRNA expression of p21WAF1 and bcl-2 was significantly higher than that in the control group(P < 0.01), while the mRNA expression of cyclinD1,bax and MCM-2 was significantly lower than that in the control group(P < 0.01 or P < 0.05). Conclusions PC-1NTP resulted in G0/G1 phase arrest and elicited an attenuating effect on the proliferation and apoptosis of cystic-lining epithelial cells, which may be realized through regulating the expression of G1/S checkpoint regulation factor cyclinD1/p21WAF1 and apoptosis regulating protein bcl-2/bax. PC-1NTP may be a new prospective maneuver in the treatment of ADPKD.

关键词

常染色体显性多囊肾病 / 细胞周期 / 多囊蛋白1

Key words

Autosomal dominant polycystic kidney disease / Cell cycle / Polycystin-1

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赵海丹;孙田美;王文靖;梅长林;徐成钢;戴兵;沈学飞;张树忠;李林. 多囊蛋白1氨基端肽对常染色体显性多囊肾囊肿衬里上皮细胞增殖和凋亡的影响[J]. 中华肾脏病杂志, 2005, 21(11): 664-668.
ZHAO Hai-dan;SUN Tian-mei;WANG Wen-jing;MEI Chang-lin;XU Cheng-gang;DAI Bing;SHEN Xue-fei;ZHANG Shu-zhong;LI Lin. Evaluation of polycystin-1 N-terminal peptide on the proliferation and apoptosis of cystic-lining epithelial cells in human ADPKD[J]. Chinese Journal of Nephrology, 2005, 21(11): 664-668.

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