Publication: Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion
Issued Date
2018-08-01
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ISSN
18732968
00062952
00062952
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2-s2.0-85047081971
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical Pharmacology. Vol.154, (2018), 175-182
Suggested Citation
Jiriporn Nantavishit, Varanuj Chatsudthipong, Sunhapas Soodvilai Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion. Biochemical Pharmacology. Vol.154, (2018), 175-182. doi:10.1016/j.bcp.2018.05.005 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45087
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Title
Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion
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Abstract
© 2018 Elsevier Inc. 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.