title: 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.
abstract: 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.
authors.affiliation: Department of Nephrology, Xiangya Hospital of Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Peng
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Ning
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Xiao
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Wang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Fu
authors.forename: Jianping
authors.initials: J
authors.lastname: Ning
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D005947:Glucose; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D000880:Anthraquinones; D005947:Glucose; D020780:Matrix Metalloproteinase 9; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D019715:Tissue Inhibitor of Metalloproteinase-1; D000099200:Scaffold Protein ILK; C560822:TIMP1 protein, human; C020491:rhein