Hesperidin inhibits the epithelial to mesenchymal transition induced by transforming growth factor-ß1 in A549 cells through Smad signaling in the cytoplasm

Hesperidin, a natural compound, suppresses the epithelial-to-mesenchymal transition through the TGF-ß1/Smad signaling pathway. However, studies on the detailed effects and mechanisms of hesperidin are rare. The present study showed that, for A549 alveolar epithelial cells, the anti-proliferative effects of hesperidin occurred in a dose-dependent manner, with an IC50= 216.8 µM at 48 h. TGF-ß1 was used to activate the Smad signaling pathway and induce the epithelial to mesenchymal transition in cells. Treatment with hesperidin or SB431542 was used for antagonism of Smad pathway activation. Hesperidin inhibited the increase in ɑ-SMA and Col1ɑ-1 and the decrease in E-cadherin in a dose-dependent manner from concentration of 20 µM to 60 µM, as assessed by both ELISA and Western blotting assays; however, there was no significant effect on cellular morphological alterations. Moreover, the Western blotting assay showed that, in the cytoplasm, hesperidin and SB431542 had no significant effect on the protein expression of Smad 2, 3, 4, or 7 as well as 2/3. However, 60 µM hesperidin and SB431542 significantly decreased p-Smad2/3 protein expression. From the above results, it is concluded that hesperidin can partly inhibit the epithelial to mesenchymal transition in human alveolar epithelial cells; the effect accounts for the blockage of the phosphorylation of Smad2/3 in the cytoplasm rather than a change in Smad protein production in the cytoplasm

Effect of STAT3 gene silencing on epithelial-to-mesenchymal transition of human pancreatic cancer cells / 中华肝胆外科杂志

Objective To investigate the effect and mechanism of RNAi-mediated STAT3 gene silencing on epithelial-to-mesenchymal transition (EMT) of human pancreatic cancer cells.Methods Lentivirus vector mediating RNA interference targeting STAT3 was constructed in SW1990 cell line.The invasion ability of SW1990 cells was determined by cell invasion assay in vitro.Cell proliferation and cell cycle of SW1990 cells were also detected.The expression of EMT related genes such as STAT3,P-STAT3,Twist,Snail and E-cadherin were analyzed by reverse transcription-PCR,real-time PCR,and Western blotting.Results Silencing of STAT3 with RNAi not only markedly reduced proliferation but also greatly decreased the invasion ability of SW1990 cells.The mRNA level and protein expression of Snail decreased significantly (P ＜ 0.05),but those of E-cadherin increased significantly (P ＜ 0.05),compared to parental cells.However,no difference was on the expression of Twist in SW1990 cell line.Conclusions STAT3 signaling pathway plays an important role in the process of EMT.Silencing of STAT3 with RNAi can significantly inhibit EMT by downregulating expression of Snail and E-cadherin in pancreatic cancer cells.

Preservation of peritoneal membrane in CAPD patients / 대한내과학회지

Peritoneal membrane shows progressive thickening, fibrotic changes and neovascularization with time on PD. Peritonitis, uremia and bioincompatible dialysate solution are important causes of peritoneal fibrosis in CAPD patients. Epithelial to mesenchymal transition (EMT) is one of the important etiologic factors for the peritoneal fibrosis in CAPD patients. Low GDP group showed less EMT than conventional PD group. Adjustment of peritoneal growth factor for dialysate CA125 revealed significant association with EMT suggesting that fibroblastoid transition from HPMC could be affected by the amount of intraperitoneal VEGF per unit mass of HPMC. There was significant improvement in both degree of EMT and D-CA125 at 6th and 12th months after switching from high GDP solution to low GDP solution. Application of icodextrin solution showed preservation of the peritoneum, like less EMT and high mesothelial bulk mass. In conclusion, therapy with low GDP solution including icodextrin may positively impact on preservation of the peritoneal membrane via reduced EMT.