N-(4-hydroxyphenyl)retinamide inhibitscystogenesis by polycystic epithelial cell lines in vitro

Abstract Primairy tubular epithelial cells develop spherical monolayered cysts when cultured in collagen I matrix, a model that has been used to study the mechanism 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 of polycystic kidney cells. Number, dimension and submicroscopical characteristics of cysts were evaluated after 2 and 4 weeks from treatment with HPR. A marked inhibitory effect of HPR on cystogenesis was found at concentration of 1μM, while a complete block was observed at concentration between 5 and 10 μM. Furthermore, treatment with HPR of already formed cysts resulted in their disruption. HPR at 10 μM also induced apoptosis of several tubular epithelial cell models suggesting a correlation between the two phenomena. Taken together these observations demonstrate that HPR blocks cystogenesis 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.