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KMID : 0359920140330020073
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Korean Journal of Nephrology
2014 Volume.33 No. 2 p.73 ~ p.78
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Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease
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Lee Seung-Hun
Somlo Stefan
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Abstract
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The primary cilium of renal epithelia acts as a transducer of extracellular stimuli.
Polycystin (PC)1 is the protein encoded by the PKD1 gene that is responsible for the
most common and severe form of autosomal dominant polycystic kidney disease
(ADPKD). PC1 forms a complex with PC2 via their respective carboxy-terminal tails.
Both proteins are expressed in the primary cilia. Mutations in either gene affect the
normal architecture of renal tubules, giving rise to ADPKD. PC1 has been proposed
as a receptor that modulates calcium signals via the PC2 channel protein. The effect
of PC1 dosage has been described as the rate-limiting modulator of cystic disease.
Reduced levels of PC1 or disruption of the balance in PC1/PC2 level can lead to the
clinical features of ADPKD, without complete inactivation. Recent data show that
ADPKD resulting from inactivation of polycystins can be markedly slowed if
structurally intact cilia are also disrupted at the same time. Despite the fact that
no single model or mechanism from these has been able to describe exclusively the
pathogenesis of cystic kidney disease, these findings suggest the existence of a novel
cilia-dependent, cyst-promoting pathway that is normally repressed by polycystin
function. The results enable us to rethink our current understanding of genetics and
cilia signaling pathways of ADPKD.
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KEYWORD
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Autosomal dominant polycystic kidney disease Calcium Cilia Polycystin-1, Polycystin-2
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