<p>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, <i>Pkd1</i> 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.</p
