整合素连接激酶抑制剂QLT0267对肾小管上皮细胞转分化的影响  

Effect of integrin-linked kinase inhibitor QLT0267 on tubular epithelial-myofibroblast transdifferentiation of HK-2 cells

作　　者：林智峰[1] 贾林[2] 赵丹[1] 马莉[2] 唐玉玲[2] 杨锐[2] 杨晓萍[1] 

机构地区：[1]石河子大学医学院第一附属医院肾病科,新疆石河子832008 [2]石河子大学医学院,新疆石河子832008

出　　处：《中国现代医学杂志》2016年第17期39-44,共6页China Journal of Modern Medicine

基　　金：石河子大学科学技术研究发展计划基金(No:2013ZRKXYQ-YD16)

摘　　要：目的观察不同浓度整合素连接激酶(ILK)抑制剂QLT0267在高糖下诱导人近端肾小管上皮细胞-肌成纤维细胞转分化(TEMT)的作用。方法体外培养人近端肾小管上皮细胞,分为4组:对照组、高糖组、QLT0267组、高渗组,干预48h。逆转录聚合酶链式反应检测纤维粘连蛋白(FN)m RNA及α-平滑肌肌动蛋白(α-SMA)m RNA的表达,Western blot检测ILK、蛋白激酶B(AKT)、磷酸化-蛋白激酶B(P-AKT)及α-SMA的表达,比较组间差异,探讨QLT0267对近端TEMT过程的影响。结果 130 mmol/L高糖可以上调人近端肾小管上皮细胞细胞中ILK、P-AKT、FN、α-SMA的表达。230 mmol/L甘露醇不能引起人近端肾小管上皮细胞细胞中ILK、P-AKT、FN、α-SMA表达变化。310μmol/L QLT0267抑制高糖诱导的人近端肾小管上皮细胞细胞AKT、FN及α-SMA的m RNA和蛋白表达。结论 130 mmol/L葡萄糖可以诱导人近端TEMT。2QLT0267通过抑制人近端肾小管上皮细胞细胞中ILK下游AKT的活化,进而抑制FN及α-SMA的表达,10μmol/L QLT0267可以抑制人近端TEMT。Objective To observe the effect of different concentrations of an inhibitor of integrin-linked ki- nase （ILK） QLT0267 in process of high glucose-induced tubular epithelial-myofibroblast transdifferentiation （TEMT）. Methods The cultured human renal tubular epithelial cells （HK-2） were divided into control group, high-glucose group, QLT0267 group and D-mannitol group, and cultured for 48 hours. RT-PCR was used to test the expressions of fibroneetin （FN） mRNA and a-smooth muscle actin （a-SMA） mRNA. The ILK, AKT, p-AKT and a-SMA protein expressions were detected by Western blot. The differences among the groups were observed, and then the role of QLT0267 in the process of TEMT was explored. Results The expressions of p-AKT, ILK, FN and a-SMA in the HK-2 cells were up-regulated after 30 mmol/L glucose intervention for 48 h. However, 30 mmol/L D-mannitol did not change the expression of p-AKT, ILK, FN or a-SMA in the HK-2 cells after 48 h. QLT0267 at a concentration of 10 μmol/L inhibited the mRNA and protein expres- sions of AKT, FN and a-SMA in the high glucose-induced HK-2 cells. Conclusions Glucose can lead toTEMT in HK-2 cells at a concentration of 30 mmol/L, while 30 mmol/L D-mannitol can not. QLT0267 can prevent activation of AKT in the downstream of ILK, thereby reduce the expression of FN and a-SMA and delay the process of TEMT in the HK-2 cells at concentration of 10μmol/L.

关 键 词：转分化 近端小管上皮细胞 整合素连接激酶 QLT0267 

分 类 号：R692[医药卫生—泌尿科学]