Thiazolidinediones inhibit MDCK cyst growth through disrupting oriented cell division and apicobasal polarity.

ABSTRACT: Thiazolidinediones have been reported to retard cystic disease in rodent models by uncertain mechanisms. We hypothesized that their major effect in retarding cystogenesis was through inhibiting cell proliferation or stimulating apoptosis. In the Madin-Darby canine kidney cell (MDCK) model, rosiglitazone inhibited cyst growth in a time- and dose-dependent manner and this was accompanied by a reduction in basal proliferation and an increase in apoptosis. Unexpectedly, we also observed a striking abnormality in lumen formation resulting in a characteristic multiple lumen or loss of lumen phenotype in treated cells at doses which did not inhibit cell proliferation. These changes were preceded by mislocalization of gp135 and Cdc42, misorientation of the mitotic spindle, and retardation in centr

SUBMITTER: Mao Z 

PROVIDER: S-EPMC3119142 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature