Impact of low glucose degradation product bicarbonate/lactate-buffered dialysis solution on the epithelial-mesenchymal transition of peritoneum.
BACKGROUND
Epithelial-mesenchymal transition (EMT) is important in the development of peritoneal fibrosis. Glucose degradation products (GDPs) may induce EMT in human peritoneal mesothelial cells (HPMCs).


METHODS
The effects of individual GDPs and GDPs derived from peritoneal dialysis fluid (PDF) in both HPMCs and peritoneal membranes were evaluated. EMT was assessed with alpha-smooth muscle actin (alpha-SMA) and E-cadherin.


RESULTS
In vitro, alpha-SMA protein and mRNA levels increased in the presence of the GDPs (formaldehyde, glyoxal, methylglyoxal, and 3-deoxyglucosone), and E-cadherin decreased. Changes in the EMT markers were most prominent after exposure to 3-deoxyglucosone. Changes in both alpha-SMA and E-cadherin protein levels were less with low (L)-GDP bicarbonate/lactate-buffered PDF compared to high (H)-GDP PDF. In the rat model after 8 weeks' PDF infusion, the alpha-SMA/E-cadherin mRNA ratio increased in the H-GDP group compared with the L-GDP group (p < 0.05). The peritoneum in the H-GDP group tended to be thicker (p = 0.052) and had more blood vessels than that in the L-GDP group (p < 0.05). Tissue staining for TGF-beta1 decreased in the L-GDP group. Dual-stained cytokeratin and alpha-SMA-positive myofibroblasts in the submesothelial layer were more prominent in the H-GDP group.


CONCLUSIONS
GDPs found in PDF induce EMT of HPMCs, which is associated with peritoneal fibrosis and vascularization. Conversely, L-GDP PDF reduces EMT and peritoneal fibrosis.
Oh
Eun-Joo
EJ
Division of Nephrology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
Ryu
Hye-Myung
HM
Choi
Soon-Youn
SY
Yook
Ju-Min
JM
Kim
Chan-Duck
CD
Park
Sun-Hee
SH
Chung
Ho-Young
HY
Kim
In-San
IS
Yu
Min-A
MA
Kang
Duk-Hee
DH
Kim
Yong-Lim
YL
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D015312:Hemodialysis Solutions; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology*; D010537:Peritoneum / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis
D001639:Bicarbonates; D015312:Hemodialysis Solutions; D019344:Lactic Acid; D005947:Glucose