title: Cystic gene dosage influences kidney lesions after nephron reduction.
abstract: Cystic kidney disease is characterized by the progressive development of multiple fluid-filled cysts. Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to renal failure. The most frequent form of this disease is the inherited polycystic kidney disease (PKD). Experimental models of PKD showed that an increase of cellular proliferation and apoptosis as well as defects in apico-basal and planar cell polarity or cilia play a critical role in cyst development. However, little is known about the mechanisms and the mediators involved in acquired cystic kidney diseases (ACKD). In this study, we used the nephron reduction as a model to study the mechanisms underlying cyst development in ACKD. We found that tubular dilations after nephron reduction recapitulated most of the morphological features of ACKD. The development of tubular dilations was associated with a dramatic increase of cell proliferation. In contrast, the apico-basal polarity and cilia did not seem to be affected. Interestingly, polycystin 1 and fibrocystin were markedly increased and polycystin 2 was decreased in cells lining the dilated tubules, whereas the expression of several other cystic genes did not change. More importantly, Pkd1 haploinsufficiency accelerated the development of tubular dilations after nephron reduction, a phenotype that was associated to a further increase of cell proliferation. These data were relevant to humans ACKD, as cystic genes expression and the rate of cell proliferation were also increased. In conclusion, our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes involved in PKD is also important in ACKD.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Corre
authors.forename: Amandine
authors.initials: A
authors.lastname: Viau
authors.forename: Martine
authors.initials: M
authors.lastname: Burtin
authors.forename: Khalil
authors.initials: K
authors.lastname: El-Karoui
authors.forename: Yvette
authors.initials: Y
authors.lastname: Cnops
authors.forename: Sara
authors.initials: S
authors.lastname: Terryn
authors.forename: Huguette
authors.initials: H
authors.lastname: Debaix
authors.forename: Sophie
authors.initials: S
authors.lastname: Bérissi
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Fabiola
authors.initials: F
authors.lastname: Terzi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016764:Cell Polarity; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D018628:Gene Dosage; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009392:Nephrectomy; D009399:Nephrons / Q000473:pathology*; D007690:Polycystic Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics; D050396:TRPP Cation Channels / Q000172:deficiency / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; D050396:TRPP Cation Channels; C484365:Pkhd1 protein, mouse