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.

Regulation of transforming growth factor β‑mediated epithelial‑mesenchymal transition of lens epithelial cells by c‑Src kinase under high glucose conditions

“…EMT is a process by which epithelial cells lose their original characteristics and gain mesenchymal cell properties during specific physiological and pathological stages, including organ fibrosis (33,34). Previous studies on the EMT of renal cells cultured in HG conditions (30 or 60 mM) demonstrated significant increases of α-SMA and decreases of E-cadherin (33,34). It was also reported that EMT is the primary factor in the pathogenesis of renal fibrosis, in which TGF-β and c-Src are key inducing factors (35)(36)(37)(38).…”

Tubular cell phenotype in HIV-associated nephropathy: Role of phospholipid lysophosphatidic acid

“…Overexpression of ILK correlated to aberrant expression in EMT markers such as SNAIL, in oral squamous cell carcinoma [23]. ILK has been implicated in high glucose-induced renal tubular cell injury [24]. Small interfering RNA targets ILK inhibited cancer metastasis [25].…”

Chinese medicine for diabetic kidney disease in China

“…The anthraquinones rhein and emodin are the primary active compounds in rhubarb. Rhein has been shown to prevent kidney damage by downregulating the wnt/β‐catenin signalling pathway, upregulating SIRT1, decreasing epithelial–mesenchymal transition and ameliorating dyslipidaemia . Emodin has been found to reduce glycation of proteins and decrease mesangial cell proliferation via inhibiting cFLIP, TGF‐β1and the p38MAPK pathway …”