Galectin-1在高糖腹透液诱导人腹膜间皮细胞转分化中的作用  

Role of galectin-1 on epithelial-to-mesenchymal transition induced by high glucose peritoneal dialysate in human peritoneal mesothelial cells

作　　者：刘映红[1] 戴洪勤[1] 刘伏友[1] 孙林[1] 肖力[1] 刘虹[1] 

机构地区：[1]中南大学湘雅二医院肾内科,中南大学肾脏病研究所,长沙410011

出　　处：《中南大学学报（医学版）》2012年第2期190-196,共7页Journal of Central South University ：Medical Science

摘　　要：目的:研究人腹膜间皮细胞(human peritoneal mesothelial cells,HPMCs)中galectin-1的表达和在高糖腹透液(peritoneal dialysate solution,PDS)刺激下galectin-1表达的变化及其与上皮细胞-间充质细胞转分化(epithelial-to-mesenchymal transition,EMT)的关系。方法:以HPMCs为研究对象,实验分为:正常对照组(5.5 mmol/L葡萄糖),含1.5%葡萄糖的PDS(1.5%PDS)组,2.5%PDS组及4.25%PDS组。培养48 h后,采用实时定量PCR和Western印迹检测galectin-1,vimentin和zo-1 mRNA和蛋白的表达水平,分析galectin-1与vimentin和zo-1表达的相关性。使用阳离子脂质体转染galectin-1 siRNA至HPMCs内,实验分为:正常对照组(5.5mmol/L葡萄糖),高糖组(4.25%PDS)和转染组(galectin-1 siRNA+4.25%PDS)。观察galectin siRNA干预后vimentin和zo-1 mRNA和蛋白的表达水平。结果:不同浓度PDS刺激HPMCs 48 h后,与对照组比,galectin-1mRNA表达上调,尤以4.25%PDS组明显(P<0.05),其蛋白水平的表达均明显上调(P<0.05),且具有浓度依赖性;同时vimentin mRNA表达上调,以2.5%PDS组和4.25%PDS组更明显(P<0.05),其蛋白水平的表达均明显上调(P<0.05);而zo-1 mRNA和蛋白水平的表达均明显下调(P<0.05)。不同浓度高糖PDS刺激下galectin-1 mRNA和蛋白表达水平与vimentin mRNA和蛋白表达水平呈正相关(P<0.05);与zo-1 mRNA和蛋白表达水平呈负相关(P<0.05)。Galectin-1 siRNA干预后vimentin mRNA和蛋白水平的表达较高糖组明显下调(P<0.05),而zo-1 mRNA和蛋白水平的表达较高糖组明显上调(P<0.05)。结论:Galectin-1与高糖PDS诱导的HPMCs EMT相关,galectin-1 siRNA能够抑制高糖PDS诱导的HPMCs转分化。Galectin-1可能参与腹膜纤维化的发生环节,成为防治腹膜纤维化的新靶点。Objective： To investigate the expression of galectin-1 with the stimulation of peritoneal dialysis solution （PDS） and its role in the epithelial-to-mesenchymal transition （EMT） in human peritoneal mesothelial cells （HPMCs）. Methods： HPMCs were stimulated with PDS containing different concentrations of high glucose （1.5%, 2.5%, and 4.25%）. After 24 h, mRNA and protein expressions of galectin-1,vimentin, andzo-1 were analyzed with real-time PCR and Western blot, respectively. Liposome transfected siRNA technique was used to knock down the expression of galectin-1 and the effect of galectin-1 siRNA on the EMT of HPMCs was also observed under 4.25% PDS condition. Results： mRNA expression of galectin-1 in HPMCs increased in PDS groups, especially in group with 4.25% PDS （P〈0.05）. Protein expression of galectin-1 in HPMCs signi cantly increased in PDS groups with a dose dependent manner （P〈0.05）.Expression of vimentin in HPMCs significantly increased in PDS groups, especially in groups of 2.5% PDS and 4.25% PDS （P〈0.05）, but zo-1 expression markedly decreased （P〈0.05）.The expression of galectin-1 correlated positively with vimentin （P〈0.05） but negatively with zo-1 （P〈0.05）. Expression of vimentin in groups of 4.25% PDS was markedly inhibited （P〈0.05） by galectin-1 siRNA, whereas zo-1 expression was signi cantly increased （P〈0.05）. Conclusion： Galectin-1 can mediate high glucose PDS-induced EMT in HPMCs and may be a new target for the prevention and treatment of peritoneal brosis.

关 键 词：GALECTIN-1 高糖 腹透液 上皮细胞-间充质细胞转分化 SIRNA 

分 类 号：R459.5[医药卫生—治疗学]