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Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion

机译:Lansoprazole通过抑制细胞增殖和液体分泌来减少多囊肾病中的肾囊肿

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Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) is mediated by abnormal cyst-ling cell proliferation and fluid accumulation. Liver X receptor (LXR)-activating ligands suppresses renal cyst enlargement by modulation of cysticfibrosis transmembrane conductance regulator (CFTR)mediated fluid accumulation. Lansoprazole has been reported as agonist of LXR, and shows an anti-proliferative effect in cancer cells. Here, lansoprazole's pharmacological effect and underlying mechanism on renal cyst development and expansion in in vitro; human ADPKD cyst-lining epithelial cell line and Type I Mardin Darby Canine Kidney (MDCK) cells, and in vivo models was investigated. Lansoprazole inhibited cyst development via inhibition of cell proliferation. In renal cells, lansoprazole's anti-proliferative effect was mediated by inhibition of mTOR/S6K and extracellular signal-regulated kinase (ERK) signaling proteins. In addition, lansoprazole inhibited CFTR-mediated fluid secretion via reduction of CFTR protein expression. In PCK rats, administering lansoprazole (50 mg/kgBW) for 4 weeks produced significant decreases in the cystic area and improved renal function by reduction of plasma creatinine and blood urea nitrogen. Inhibition of mTOR/S6K, ERK, and CFTR protein expression was observed in PCK rat kidney following lansoprazole treatment. The findings point to potential therapeutic application of lansoprazole in ADPKD.
机译:肾囊肿促进常染色体显性多囊肾疾病(ADPKD)的扩张是通过异常囊肿细胞增殖和流体积累的介导。肝X受体(LXR) - 活化配体通过调节囊泡纤维化跨膜电导调节剂(CFTR)介导的流体积聚来抑制肾囊肿肿大。 Lansopazole已被称为LXR的激动剂,并显示癌细胞中的抗增殖作用。这里,兰辛拉唑的药理效应和肾囊肿开发和体外膨胀的潜在机制;研究人ADPKD囊肿上皮细胞系和I型Mardin Darby犬肾(MDCK)细胞,以及体内模型。 LansoLazole通过抑制细胞增殖抑制囊肿开发。在肾细胞中,通过抑制MTOR / S6K和细胞外信号调节激酶(ERK)信号蛋白来介导LansoPrazole的抗增殖效果。此外,LansoLazole通过降低CFTR蛋白表达抑制CFTR介导的流体分泌。在PCK大鼠中,施用兰烷唑(50mg / kgbW)4周产生囊性区域的显着降低,通过减少血浆肌酐和血尿尿素氮来改善肾功能。在LansoLazole处理后,在PCK大鼠肾脏中观察到MTOR / S6K,ERK和CFTR蛋白表达的抑制作用。该研究结果指出了兰沙拉唑在ADPKD中的潜在治疗应用。

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