Faculty Opinions recommendation of HGF and BMP-7 ameliorate high glucose-induced epithelial-to-mesenchymal transition of peritoneal mesothelium.

Background. Epithelial-to-mesenchymal transition (EMT) is thought to play a significant role in the advancement to chronic kidney disease and contributes to the deposition of extracellular matrix proteins and renal fibrosis relating to diabetic nephropathy. Method. We studied the effect of Nrf2-HO-1 signaling on high-glucose- (HG-) induced EMT in normal human tubular epithelial cells, that is, HK2 cells. In short, we treated HK2 cells with HG and sulforaphane (SFN) as an Nrf2 activator. EMT was evaluated by the expression activity of the epithelial marker E-cadherin and mesenchymal markers such as vimentin and fibronectin. Results. Exposure of HK2 cells to HG (60 mM) activated the expression of vimentin and fibronectin but decreased E-cadherin. Treatment of HK2 cells with SFN caused HG-induced attenuation in EMT markers with activated Nrf2-HO-1. We found that SFN decreased HG-induced production of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and inhibitory phosphorylation of serine/threonine kinase glycogen synthase kinase-3β (GSK-3β) at serine 9. Subsequently, these signaling led to the downregulation of the Snail-1 transcriptional factor and the recovery of E-cadherin. Conclusion. The present study suggests that Nrf2-HO-1 signaling has an inhibitory role in the regulation of EMT through the modulation of ROS-mediated PI3K/Akt/GSK-3β activity, highlighting Nrf2-HO-1 and GSK-3β as potential therapeutic targets in diabetic nephropathy.

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Activation of autophagy inhibits epithelial to mesenchymal transition process of human lens epithelial cells induced by high glucose conditions

Cellular Signalling ◽

10.1016/j.cellsig.2020.109768 ◽

2020 ◽

Vol 75 ◽

pp. 109768 ◽

Cited By ~ 1

Author(s):

Ji Li ◽

Wei Ye ◽

Wenqin Xu ◽

Tianfang Chang ◽

Luning Zhang ◽

...

Keyword(s):

Epithelial Cells ◽

High Glucose ◽

Epithelial To Mesenchymal Transition ◽

Transition Process ◽

Human Lens ◽

Lens Epithelial Cells ◽

Mesenchymal Transition ◽

Human Lens Epithelial Cells

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Characterization of Epithelial-to-Mesenchymal Transition of Mesothelial Cells in a Mouse Model of Chronic Peritoneal Exposure to High Glucose Dialysate

Peritoneal Dialysis International ◽

10.1177/089686080802805s06 ◽

2008 ◽

Vol 28 (5_suppl) ◽

pp. 29-33 ◽

Cited By ~ 13

Author(s):

Luiz S. Aroeira ◽

Jesús Loureiro ◽

Guadalupe T. González-Mateo ◽

Vanessa Fernandez-Millara ◽

Gloria del Peso ◽

...

Keyword(s):

Mouse Model ◽

High Glucose ◽

Sequential Analysis ◽

Epithelial To Mesenchymal Transition ◽

Smooth Muscle Actin ◽

Mesothelial Cells ◽

Dependent Manner ◽

Peritoneal Membrane ◽

Mesenchymal Transition ◽

Peritoneal Dialysis Fluid

Animal models of peritoneal dialysis fluid (PDF) exposure are key tools in the study of mechanisms involved in alterations of the peritoneal membrane and in the design of therapies. We recently developed a mouse model of chronic peritoneal exposure to high glucose dialysate. Herein, we make a sequential analysis of the effects of glucose-based PDF on mouse peritoneal membrane and on mesothelium. We demonstrate that chronic exposure to PDF induces thickness and fibrosis of the peritoneal membrane in a time-dependent manner. We also show that mesothelial cells progressively detach and lose cytokeratin expression. In addition, we demonstrate that some mesothelial cells invade the submesothelial space, where they appear as cytokeratin- and alpha-smooth muscle actin-positive cells. These findings demonstrate that epithelial-to-mesenchymal transition (EMT) of mesothelial cells takes place in mouse peritoneum exposed to PDF, validating this model for the study of effects of drugs on the EMT process as a therapy for peritoneal deterioration.

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