Abstract: TH-PO359

Effects of High-Glucose Induced Epithelial to Mesenchymal Transition by Sulforaphan in Human Renal Tubule Cells

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Authors

  • Song, Young woong, EUL-JI University hospital R Korea Daejeon, Dae-jeon, Korea (the Republic of)
  • Shin, Jongho, Eulji Hospital, Daejeon, Korea (the Republic of)
  • Kim, Kyeong Min, Eulji medical center, Daejeon, Korea (the Republic of)
Background

Epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in the kidney is associated with the progression of renal tubulointerstitial fibrosis and contributes to the renal matrix protein accumulation that is associated with diabetic nephropathy.

Methods

In this study, we examined the role of Nrf2 and heme oxygenase-1 (HO-1) protein on EMT induced by high glucose (HG) in the human renal tubular epithelial cells (HK2 cells). We treated HK2 cells with HG and Nrf2 activator, Sulforaphan. EMT was assessed by the expression of mesenchymal markers such as α-smooth muscle actin (α-SMA) and vimentin, and epithelial marker, E-cadherin.

Results

Exposure of HK2 cells to HG (50 mM) resulted in an increase of the expression of α-SMA and vimentin, and was associated with a decrease in the expression of E-cadherin. Treatment of HK2 cells with Nrf2 activator, Sulforaphan, showed a dosage-dependent amelioration of HG induced changes in markers of EMT with an increase of HO-1 expression. We found that SFN ameliorated experimental diabetic nephropathy, at least in part, via GSK3β /Nrf2 signaling pathway. We observed NRF2 activator inhibited high glucose-induced generation of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and phosphoratory inhibition of serine/therionine kinase gycogen synthase kinase-3β (GSK-3β) at serine 9. These signaling resulted in the down-regulation of Snail transcriptional factor and recovery of E-cadherin. The Nrf2 activation attenuates high glucose-induced epithelial-to-mesenchymal transition via modulation of GSK-3β activity in human renal tubular cells.

Conclusion

Taken together, our results suggest that Nrf2-HO-1 has a critical role in the regulation of EMT through modulation of GSK-3β activity, highlighting Nrf2-HO-1 and GSK-3β as a potential therapeutic target in diabetic nephropathy.