摘要
目的:探讨高糖环境下缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF1α)-肾损伤分子-1(kidney injury molecule-1,KIM1)信号通路对糖尿病肾病肾间质纤维化的影响。方法:体外培养人肾小管上皮细胞,分为正常对照组、高糖组、转染对照组、HIF1α转染组和KIM1转染组:(1)正常对照组(5.6 mmol/L葡萄糖);(2)高糖组(30 mmol/L葡萄糖);(3)转染对照组(30 mmol/L葡萄糖+乱序的非特异性siRNA);(4)HIF1α转染组(30 mmol/L葡萄糖+HIF1αsiRNA);(5)KIM1转染组(30 mmol/L葡萄糖+KIM1siRNA)。分析HIF1α、KIM1、纤维连接蛋白(fiber link protein,FN)和Ⅰ型胶原蛋白(Ⅰtype COLlagen,COL-Ⅰ)的表达。结果:高糖组的的HIF1α、KIM1、FN、COL-Ⅰ的蛋白相对表达量和mRNA相对表达量明显高于正常对照组,差异具有统计学意义(P<0.05)。HIF1α转染组的HIF1α、KIM1、FN、COL-Ⅰ的蛋白相对表达量和mRNA相对表达量明显低于转染对照组,差异具有统计学意义(P<0.05)。KIM1转染组的KIM1、FN、COL-Ⅰ的蛋白相对表达量和mRNA相对表达量明显低于转染对照组,差异具有统计学意义(P<0.05)。KIM1转染组的HIF1α的蛋白相对表达量和mRNA相对表达量与转染对照组比较并无明显变化。结论:高糖环境下HIF1α-KIM1信号通路能够通过调控FN、COL-Ⅰ等相关蛋白的表达影响糖尿病肾病肾间质纤维化的发生和发展。
Objective：To investigate the effect of hypoxia-inducible factor-1α（KIF1）signaling pathway on renal interstitial fibrosis in diabetic nephropathy.Methods：Human renal tubular epithelial cells were cultivated in vitro,and divided into normal control group,high sugar,transfection control group,HIF1 alpha transfection group and KIM1 transfection group：normal control group（5.6 tendency/L glucose）;the high sugar group（30 tendency/L glucose）;transfection in the control group（30 tendency/L glucose ＋ out-of-order1 nonspecific siRNA）;HIF1 alpha transfection group（30 tendency/L glucose ＋ HIF1 alpha siRNA）;KIM1 transfection group（30 tendency/L glucose ＋ KIM1 siRNA）.HIF1 alpha,KIM1,fiber link protein（FN） and Ⅰ type COLlagen（COL-Ⅰ）expressions were analyzed.Results：The relative expression and relative expression of HIF1α,KIM1,FN and COL-Ⅰ in high glucose group were significantly higher than those in normal control group（P〈0.05）.The relative expression of HIF1α,KIM1,FN,COL-Ⅰ in HIF1α-transfected group was significantly lower than that in transfected control group（P〈0.05）.The relative expression of KIM1,FN and COL-Ⅰ in KIM1 transfected group was significantly lower than that in transfected control group（P〈0.05）.The relative expression of HIF1αprotein and relative expression of mRNA of KIM1 transfected group did not change significantly compared with that in transfected control group.Conclusion：HIF1α-KIM1 signaling pathway can influence the occurrence and development of renal interstitial fibrosis in diabetic nephropathy by regulating the expression of FN,COL-Ⅰ and other related proteins.
出处
《重庆医科大学学报》
CSCD
北大核心
2017年第12期1626-1630,共5页
Journal of Chongqing Medical University
关键词
高糖
缺氧诱导因子-1Α
肾损伤分子-1
糖尿病肾病
肾间质纤维化
high glucose
hypoxia-indueible factor-lot
kidney injury molecule-1
diabetic nephropathy
renal interstitial fibrosis
