Are ex vivo mesothelial cells representative of the in vivo transition from epithelial-to-mesenchymal cells in peritoneal membrane?
BACKGROUND
We investigated whether ex vivo mesothelial cells found in peritoneal dialysis (PD) effluents were representative of the in vivo epithelial-to-mesenchymal transition (EMT) in peritoneal membrane.


METHODS
Thirty-six male Sprague-Dawley rats were equally divided into three groups: Group C (control), no PD; Group D, infused with 4.25% Dianeal and Group P, infused with 4.25% Physioneal. PD infusions (25 mL) were given twice daily for 8 weeks. The in vivo study included morphometric analyses performed on the peritoneal membranes of tissue specimens obtained at the end of the study. The ex vivo study included peritoneal mesothelial cells collected from PD effluent and cultured to confluence. Cells were scored with light microscopy.


RESULTS
PD for 8 weeks induced significant EMT. The in vivo expression of EMT markers (α-smooth muscle actin:E-cadherin ratio, matrix metalloproteinase-2 and Snail) was higher in Group D than in Group P. However, ex vivo EMT marker expression was similar in cells derived from Groups D and P. A significant correlation was observed among in vivo EMT markers. Moreover, the ex vivo cell score increased with time on PD. However, changes in the ex vivo cell score did not correlated with changes in the in vivo EMT marker expression. Furthermore, we found no correlation between ex vivo and in vivo cells in the expression of EMT markers.


CONCLUSIONS
In this animal study, ex vivo findings did not reflect the in vivo EMT changes in the peritoneum. It may be necessary to improve the current methodology for ex vivo studies.
Department of Internal Medicine, CHA Gumi Medical Center, CHA University, Gumi-si, Korea.
Ji-Hyung
JH
Cho
Jun-Young
JY
Do
Eun-Joo
EJ
Oh
Hye-Myung
HM
Ryu
So-Young
SY
Park
San-Ok
SO
Kim
Seung-Hyea
SH
Hyun
Hye-Jin
HJ
Seo
Gun-Hyun
GH
Kim
Ji-Young
JY
Choi
Chan-Duck
CD
Kim
Sun-Hee
SH
Park
Yong-Lim
YL
Kim
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D015314:Dialysis Solutions / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D023421:Models, Animal; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D015820:Cadherins; D015314:Dialysis Solutions; D020778:Matrix Metalloproteinase 2; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C000604450:Snai2 protein, rat; C498862:Acta2 protein, rat