N-(4-hydroxyphenyl) retinamide inhibits cystogenesis by polycystic epithelial cell lines in vitro.
Primary tubular epithelial cells develop spherical monolayered cysts when cultured in collagenI 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 1 microM, while a complete block was observed at concentration between 5 and 10 microM. Furthermore, treatment with HPR of already formed cysts resulted in their disruption. HPR at 10 microM 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.
Altieri
P
P
Department of Nephrology, Giannina Gaslini Institute, Genoa, Italy.
Caridi
G
G
Chiesa
V
V
Ponzoni
M
M
Ghiggeri
G M
GM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D017313:Fenretinide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology; D008954:Models, Biological; D007690:Polycystic Kidney Diseases / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D051381:Rats
D017313:Fenretinide