Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion
© 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 t...
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th-mahidol.450872019-08-28T13:49:24Z Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion Jiriporn Nantavishit Varanuj Chatsudthipong Sunhapas Soodvilai Mahidol University Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics © 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. 2019-08-23T10:29:44Z 2019-08-23T10:29:44Z 2018-08-01 Article Biochemical Pharmacology. Vol.154, (2018), 175-182 10.1016/j.bcp.2018.05.005 18732968 00062952 2-s2.0-85047081971 https://repository.li.mahidol.ac.th/handle/123456789/45087 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85047081971&origin=inward |
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Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics Jiriporn Nantavishit Varanuj Chatsudthipong Sunhapas Soodvilai Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
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© 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. |
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Mahidol University |
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Mahidol University Jiriporn Nantavishit Varanuj Chatsudthipong Sunhapas Soodvilai |
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Jiriporn Nantavishit Varanuj Chatsudthipong Sunhapas Soodvilai |
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Jiriporn Nantavishit |
title |
Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
title_short |
Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
title_full |
Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
title_fullStr |
Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
title_full_unstemmed |
Lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
title_sort |
lansoprazole reduces renal cyst in polycystic kidney disease via inhibition of cell proliferation and fluid secretion |
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2019 |
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https://repository.li.mahidol.ac.th/handle/123456789/45087 |
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1763492306215763968 |