N-(4-hydroxphenyl) retinamide inhibits cystogenesis by polycystic epithelial cell lines in vitro

Primary tubular epithelial cells develop spherical monolayered cysts when c ultured in collagenI matrix, a model that has been used to study the mechan ism of cystogenesis. In an attempt to block cystogenesis, we have evaluated the effect of N-(4-hydroxyphenyl) retinamide (HPR), a synthetic derivative of retinoic acid, on both formation and growth of cysts in a human model o f polycystic kidney cells. Number, dimension and submicroscopical character istics of cysts were evaluated after 2 and 4 weeks from treatment with HPR. A marked inhibitory effect of HPR on cystogenesis was found at concentrati on of 1 mu M, while a complete block was observed at concentration between 5 and 10 mu M. Furthermore, treatment with HPR of already formed cysts resu lted in their disruption. HPR at 10 mu M also induced apoptosis of several tubular epithelial cell models suggesting a correlation between the two phe nomena. Taken together these observations demonstrate that HPR blocks cysto genesis by polycystic kidney cells "in vitro" and that it also reverts the fate of already formed cysts. Apoptosis may be the mechanism which mediates the inhibitory effect on cystogenesis in this model. (C) 1999 Elsevier Sci ence Inc.