Effect of lansoprazole on cyst formation and cyst enlargement of renal tubular cellsPunyawee Jintanapanya
( M.Sc. )
Polycystic kidney disease (PKD) is a genetic disorder in which cyst formation and cyst enlargement cause of abnormal cell proliferation and fluid secretion results in loss of normal function and eventually lead to renal failure. There is no specific protocol to treat this disease. Recently, liver X receptors (LXRs) have been shown to reduce cyst formation and cyst growth via CFTR-mediated chloride transport in renal collecting duct cells. The present study demonstrated the effect of lansoprazole, a FDA-approved drug reported as LXR agonist, on cyst formation and cyst enlargement on renal tubular cells. In addition, its derivatives on cyst formation and cyst growth were also investigated. The results showed that treatment of the Madin Darby canine kidney (MDCK) cells with sulfoxide R-S(=O)-R¢ (lansoprazole), sulfide R-S-R (derivative 1), sulfone R-S(=O)2-R¢(derivative 2), methoxy –OCH3 (derivative 3)and amino group –NH2 (derivative 4) increased sterol regulatory element-binding protein-1c (SREBP-1c) intensity. These results indicated that the treatment of these compounds promoted LXR activation in MDCK cells. The effects of lansoprazole and derivative 1, 3 and 4 showed the potential effects to inhibit cyst formation in MDCK cyst model. These inhibitory effects on cyst formation were likely to be a result of the reduction on cell proliferation. LXR activation of lansoprazole and its derivatives not only inhibited cyst formation but also slowed cyst enlargement. The results showed that lansoprazole and its derivatives significantly inhibited AVP induced Cl- secretion. The data suggest that lansoprazole and its derivatives could retard cyst enlargement by inhibiting CFTR-mediated chloride secretion. Moreover, the inhibitory effect on cyst formation and cyst growth of lansoprazole and its derivatives were not caused by their cytotoxicity. This novel finding was the first evidence to show that lansoprazole and its derivatives inhibit cyst formation and cysu enlargement in the renal tubular cells.