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  

Evaluation of polycystin-1 N-terminal peptide on the proliferation and apoptosis of cystic-lining epithelial cells in human ADPKD

作　　者：赵海丹[1] 孙田美[2] 王文靖[2] 梅长林[2] 徐成钢[2] 戴兵[2] 沈学飞[2] 张树忠[2] 李林[2] 

机构地区：[1]海军总医院肾内科,北京100037 [2]上海第二军医大学长征医院肾内科解放军肾脏病中心

出　　处：《中华肾脏病杂志》2005年第11期664-668,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金(30170901;30271523)国家高技术研究发展计划(863)(2002AA2Z3130)

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。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。用流式细胞仪分析细胞周期与凋亡状况。用荧光定量PCR检测细胞中细胞周期素cyclinD1、p21^(WAF1)、bax、bcl-2和小染色体维护蛋白2(MCM-2)的mRNA表达。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)。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/p21^(WAF1)和凋亡调节蛋白bcl-2/bax的表达实现的。PC-1NTP有希望成为治疗ADPKD的可选药物。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, p21^wpan, bax, bel-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 GO/ G1 phase increased, while decreased in S phase remarkably. The mRNA expression of p21^WAF1 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 GO/G1 phase arrest and elicited an attenuating effect on the proliferation and apeptosis of cystic-lining epithelial cells, which may be realized through regulating the expression of G1/S checkpoint regulation factor cyclinD1/p21^WAF1 and apeptosis regulating protein bel-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 

分 类 号：R692.1[医药卫生—泌尿科学]