Paricalcitol ameliorates epithelial-to-mesenchymal transition in the peritoneal mesothelium.
BACKGROUND
The purpose of the present study was to examine the effectiveness of paricalcitol for the prevention of epithelial-to-mesenchymal transition (EMT).


METHODS
Human peritoneal mesothelial cells (HPMCs) were cultured in media containing transforming growth factor β1 (TGF-β1) with or without paricalcitol. Forty-two male Sprague-Dawley rats were divided into three groups. In the control group, the catheter was inserted but no dialysate was infused. The peritoneal dialysis (PD) group was infused with a conventional 4.25% dialysis solution. The paricalcitol group was infused with 4.25% dialysis solution and cotreated with paricalcitol.


RESULTS
Exposure of HPMCs to TGF-β1 decreased the protein level of the epithelial cell marker and increased the expression levels of the mesenchymal markers. Cotreatment with paricalcitol increased the protein levels of the epithelial cell marker and decreased those of mesenchymal markers compared with their levels in cells treated with TGF-β1 alone. Exposure of HPMCs to TGF-β1 significantly increased the phosphorylation of Smad2 and Smad3. Cotreatment with paricalcitol significantly decreased the phosphorylation of Smad2 and Smad3 compared with that of cells treated with TGF-β1 alone. After 8 weeks of experimental PD in rats, the thickness of the peritoneal membrane in the PD group was significantly increased compared with that of the control group. Cotreatment with paricalcitol decreased peritoneal thickness.


CONCLUSIONS
The present study showed that paricalcitol attenuates the TGF-β1-induced EMT in peritoneal mesothelial cells. We suggest that paricalcitol may preserve peritoneal mesothelial cells during PD and could thus be of value for the success of long-term PD.
Division of Nephrology, Department of Internal Medicine, Yeungnam University Hospital, Daegu, Korea.
Seok Hui
SH
Kang
San Ok
SO
Kim
Kyu Hyang
KH
Cho
Jong Won
JW
Park
Kyung Woo
KW
Yoon
Jun Young
JY
Do
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004872:Ergocalciferols / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000737:chemistry; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D000199:Actins; D050071:Bone Density Conservation Agents; D015820:Cadherins; D015314:Dialysis Solutions; D004872:Ergocalciferols; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C084656:paricalcitol