白蛋白对肾小管上皮细胞转分化的影响及其分子机制  

Effect of albumin on transdifferentiation of renal tubular epithelial cells and its molecular mechanism

作　　者：白瑜[1] 于锐[1] 田密[1] 何平[1] 赵自霞[1] 张蓓茹[1] BAI Yu;YU Rui;TIAN Mi;HE Ping;ZHAO Zixia;ZHANG Beiru(Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院,沈阳110004

出　　处：《山东医药》2020年第35期22-25,共4页Shandong Medical Journal

基　　金：辽宁省自然科学基金指导计划项目(2019-ZD-0771)。

摘　　要：目的观察白蛋白对肾小管上皮细胞转分化的影响,并探讨其可能的机制。方法取对数生长期的人肾小管上皮细胞系HK-2,加入5 mg/mL人血清白蛋白(HSA)作用24 h,采用Western blotting法检测HSA作用前后细胞E钙黏素(E-cadherin)、α平滑肌肌动蛋白(α-SMA)、肾损伤分子1(KIM-1)、p-p38、p38表达。将HK-2细胞分为KIM-1沉默组和空载体对照组,分别转染KIM-1 siRNA质粒及对照空载体,转染48 h后加入5 mg/mL HSA处理24 h,检测细胞E-cadherin、α-SMA、KIM-1表达。将HK-2细胞分为SB203580+KIM-1组、KIM-1组和HSA组,SB203580+KIM-1组转染KIM-1过表达质粒48 h后给予10μmol/L p38分裂原激活蛋白激酶(p38 MAPK)特异性抑制剂SB203580处理1 h,KIM-1组转染KIM-1过表达质粒48 h,三组均加入5 mg/mL HSA作用24 h,检测细胞E-cadherin、α-SMA、KIM-1、p-p38、p38表达。结果与HSA作用前比较,HSA作用后HK-2细胞E-cadherin表达降低,α-SMA、KIM-1、p-p38表达均升高(P均<0.05),p38表达变化无统计学意义(P>0.05)。与空载体对照组比较,KIM-1沉默组E-cadherin表达升高,α-SMA、KIM-1表达均降低(P均<0.05)。KIM-1组、SB203580+KIM-1组和HSA组E-cadherin表达依次升高,α-SMA、p-p38表达均依次降低(P均<0.05),三组p38表达比较无统计学差异(P均>0.05)。SB203580+KIM-1组、KIM-1组KIM-1表达均高于HSA组(P均<0.05),SB203580+KIM-1组、KIM-1组KIM-1表达比较无统计学差异(P>0.05)。结论白蛋白可促进肾小管上皮细胞转分化,其机制可能与促进KIM-1表达进而激活p38 MAPK信号通路有关。Objective To explore the effect and the possible mechanism of albumin on transdifferentiation of renal tubular epithelial cells.Methods The renal tubular epithelial cells(HK-2 cells)in the logarithmic phase were treated with human serum albumin(HSA)5 mg/mL for 24 h.The expression of kidney injury molecule-1(KIM-1),E-cadherin,α-smooth muscle actin(α-SMA),p-p38 and p38 proteins before and after HSA treatment was detected by Western blotting.Next,the HK-2 cells were divided into two groups:KIM-1 silencing group and empty vector control group,which were transfected with KIM-1 siRNA plasmid or empty vector,respectively,then the expression of E-cadherin,α-SMA and KIM-1 was detected after treatment with HSA 5 mg/mL for 24 h.At last,the HK-2 cells were divided into three groups:SB203580+KIM-1 group,KIM-1 group,and HSA group.The cells in the SB203580+KIM-1 group were transfected with KIM-1 overexpression plasmid for 48 h and then were pretreated with 10μmol/L SB203580,a specific inhibitor of p38 mitogen-activated protein kinase(MAPK)for 1 h.The cells in the KIM-1 group were only transfected with KIM-1 overexpression plasmid for 48 h.The expression of E-cadherin,α-SMA,KIM-1,p-p38 and p38 proteins in the above three groups was detected by Western blotting after treatment with HSA 5 mg/mL for 24 h.Results The protein expression of E-cadherin decreased,α-SMA,KIM-1,and p-p38 increased in HK-2 cells treated with 5 mg/mL HSA as compared with those before HSA treatment(all P<0.05),while the change of p38 protein was statistically significant(P>0.05).Compared with the empty vector control group,the protein expression of E-cadherin increased,α-SMA and KIM-1 decreased in the KIM-1 silencing group(all P<0.05).In the KIM-1 group,SB203580+KIM-1 group and HSA group,the protein expression of E-cadherin increased in turn,α-SMA and p-p38 decreased in turn(all P<0.05),and no statistically significant difference was found in the p38 protein among three groups(P>0.05).The protein expression of KIM-1 in the SB203580+KIM-1 group and KIM

关 键 词：上皮细胞转分化 肾小管上皮细胞 白蛋白 肾损伤分子1 p38分裂原激活蛋白激酶 

分 类 号：R363.1[医药卫生—病理学]