Kang Seok Hui, Kim San Ok, Cho Kyu Hyang, Park Jong Won, Yoon Kyung Woo, Do Jun Young
Division of Nephrology, Department of Internal Medicine, Yeungnam University Hospital, Daegu, Korea.
Nephron Exp Nephrol. 2014;126(1):1-7. doi: 10.1159/000357156. Epub 2014 Jan 17.
The purpose of the present study was to examine the effectiveness of paricalcitol for the prevention of epithelial-to-mesenchymal transition (EMT).
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.
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.
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.
本研究旨在探讨帕立骨化醇预防上皮-间质转化（EMT）的有效性。
人腹膜间皮细胞（HPMC）在含有或不含有帕立骨化醇的转化生长因子β1（TGF-β1）培养基中培养。42只雄性Sprague-Dawley大鼠分为三组。对照组插入导管但不注入透析液。腹膜透析（PD）组注入传统的4.25%透析液。帕立骨化醇组注入4.25%透析液并与帕立骨化醇联合治疗。
HPMC暴露于TGF-β1可降低上皮细胞标志物的蛋白水平，并增加间质标志物的表达水平。与单独用TGF-β1处理的细胞相比，联合使用帕立骨化醇可增加上皮细胞标志物的蛋白水平，并降低间质标志物的蛋白水平。HPMC暴露于TGF-β1可显著增加Smad2和Smad3的磷酸化。与单独用TGF-β1处理的细胞相比，联合使用帕立骨化醇可显著降低Smad2和Smad3的磷酸化。大鼠进行8周实验性腹膜透析后，PD组腹膜厚度较对照组显著增加。联合使用帕立骨化醇可降低腹膜厚度。
本研究表明，帕立骨化醇可减轻TGF-β1诱导的腹膜间皮细胞EMT。我们认为，帕立骨化醇可能在腹膜透析期间保护腹膜间皮细胞，因此对长期腹膜透析的成功可能具有重要价值。
