Rhein Inhibits Integrin-Linked Kinase Expression and Regulates Matrix Metalloproteinase-9/Tissue Inhibitor of Metalloproteinase-1 Ratio in High Glucose-Induced Epithelial-Mesenchymal Transition of Renal Tubular Cell
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概要
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Studies have found overexpressed integrin-linked kinase (ILK) and disturbed matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) ratio in diabetic nephropathy epithelial-mesenchymal transition (EMT). However, the underlying mechanisms of EMT and the inhibiting effect of rhein need further understanding. The aim of this study was to investigate the possible regulating effects of ILK towards MMP-9/TIMP-1 ratio in EMT and the inhibiting effect of rhein. The characteristic epithelial marker and mesenchymal marker of EMT were examined by cytoimmunostaining, real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and Western blot. To observe the EMT inhibiting effects of rhein, specific ILK-small interfering RNA (ILK-siRNA) was used as a positive control. The results showed that in high glucose conditions, overexpression of ILK and an abnormal changing of MMP-9/TIMP-1 ratio occurred; ILK inhibition by siRNA could adjust MMP-9/TIMP-1 ratio to near normal. Meanwhile, rhein inhibited the overexpressing ILK and inhibits high glucose-induced EMT; the effect was similar to that of ILK-siRNA. The decreased expression of ILK regulated by rhein contributed to the adjustment of the MMP-9/TIMP-1 ratio. Our data indicates that rhein inhibits high glucose-induced-EMT partially through the inhibition of ILK expression and regulates the MMP-9/TIMP-1 ratio in HK-2 cells. This mechanism may be associated with rhein’s effect of ILK suppression.
著者
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Zhang Jing
Department Of Anatomy Histology & Embryology School Of Basic Medical Sciences Peking University
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Fu Shuangshuang
Department of Nephrology, Xiangya Hospital of Central South University
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Peng Linlin
Department of Nephrology, Xiangya Hospital of Central South University
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Yang Jiayi
Department of Nephrology, Xiangya Hospital of Central South University
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Ning Chen
Department of Urology, Xiangya Hospital of Central South University
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Xiao Xiangcheng
Department of Nephrology, Xiangya Hospital of Central South University
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He Dan
Department of Nephrology, Xiangya Hospital of Central South University
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Wang Xiaoyuan
Department of Nephrology, Xiangya Hospital of Central South University
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Li Zhiping
Department of Nephrology, Xiangya Hospital of Central South University
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Ning Jianping
Department of Nephrology, Xiangya Hospital of Central South University
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