CTGF反义寡核苷酸对AngⅡ诱导的人近曲肾小管上皮细胞转分化的影响  

Effect of connective tissue growth factor antisense oligonucleotide on human proximal tubular cell transdifferentiation induced by angiotensin Ⅱ

作　　者：陈珑[1] 刘必成[1] 马坤岭[1] 刘宏[1] 罗冬冬[1] 

机构地区：[1]东南大学肾脏病研究所东南大学附属中大医院,江苏南京210009

出　　处：《东南大学学报（医学版）》2006年第3期168-173,共6页Journal of Southeast University(Medical Science Edition)

基　　金：国家自然科学基金资助项目(30471732);江苏省自然科学基金资助项目(BK2002052);江苏省医学重点人才基金资助项目(RC2002072)

摘　　要：目的:探讨结缔组织生长因子(CTGF)反义寡核苷酸对血管紧张素Ⅱ(AngⅡ)诱导的肾小管细胞转分化的可能影响。方法:采用体外培养的人近曲肾小管上皮细胞株(HK2),分别观察CTGF反义寡核苷酸和AngⅡ干预细胞对细胞CTGF mRNA和蛋白质的表达、细胞内超微结构及细胞α-平滑肌肌动蛋白(α-SMA)表达的影响。结果:AngⅡ干预HK2细胞48 h后,细胞CTGF mRNA和蛋白的表达显著增高(P<0.01);AngⅡ干预96 h后,细胞超微结构显示出间质细胞样结构;这些作用都可被CTGF反义寡核苷酸显著抑制。AngⅡ可以呈时间依赖性地刺激HK2细胞表达α-SMA,这些作用可以被CTGF反义寡核苷酸显著抑制(P<0.01)。对照组错义寡核苷酸无上述作用。结论:CTGF反义寡核苷酸对AngⅡ诱导HK2细胞转分化具有显著的抑制作用,提示CTGF可能介导了AngⅡ诱导的肾小管上皮细胞转分化。Objective To investigate the effect of connective tissue growth factor antisense oligonucleotide （ CTGF AS） on Ang Ⅱ induced tubular cell transdifferentiation . Methods The influence of CTGF AS on Ang Ⅱ -induced HK2 cells CTGF mRNA and protein expression were observed by RT-PCR and confocal microscopy respectively. The effect of CTGF AS on Ang Ⅱ- induced cellular ultrastructure were observed by transmissive electronic microscope （TEM）. The expression of a-smooth action （a-SMA） were observed by immunocytochemistry. The control group was treated with scrambled oligonucleotide （SC）. Results It was shown that Ang Ⅱ signficantly induced the increasing expression of CTGF mRNA and protein （P 〈0.01, respectively）. If the cells were stimulated with Ang Ⅱ for 96 h, the cellular ultrastructure showed mesenchymal features. And these effects could be partially attenuated by CTGF AS. Ang Ⅱ significantly stimulated the expression of a-SMA in a time-dependent manner, which could be markedly attenuated by the treatment with CTGF AS （P 〈0.01, respectively）. The control group treated with SC had no such effects. Conclusion Ang Ⅱ induces the EMT of tubular epithelial cells, which can be significantly attenuated by treatment with CTGF AS. Our data have provided evidence that CTGF might be involved in the Ang Ⅱ induced tubular cell EMT.

关 键 词：人近曲肾小管上皮细胞 血管紧张素Ⅱ 结缔组织生长因子 细胞转分化 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学]