Finally, scrib and yap had a genetic interaction with pkd2 in cyst formation, and the overexpression of Scribble attenuated the down-regulation of cytoplasmic YAP in ADPKD.
Finally, we propose novel strategies for uncovering the mode of action of PC1 and PC2 and suggest means by which their dysfunction or loss of expression lead to cystogenesis and ADPKD development.
Therefore, PC2 and PC1 are functionally expressed in LCLs, which provide a model, easily obtainable from ADPKD patients, to study PKD gene expression and function.
Polycystin-1 (PC1), the PKD1 gene product, plays a critical role in renal tubule diameter control and disruption of its function causes cyst formation in human autosomal dominant polycystic kidney disease.
Thus, γ-secretase-dependent release of the PC1-CTT creates a protein fragment whose expression is sufficient to suppress ADPKD-related phenotypes in vitro and in vivo.
Finally, we propose novel strategies for uncovering the mode of action of PC1 and PC2 and suggest means by which their dysfunction or loss of expression lead to cystogenesis and ADPKD development.
ADPKD renal epithelial cells expressed high levels of polycystin-1 protein and showed increased adhesion to type I collagen by comparison with normal adult human renal epithelia that expressed little polycystin.
To determine whether the vascular expression of polycystin-2 is similar to that of polycystin-1, the expression of PKD2 mRNA and protein in cultured pig aortic VSMC was studied and immunofluorescence and immunohistochemistry were used to study the localization of polycystin-2 in cultured pig aortic VSMC, pig ascending thoracic aorta, and normal elastic and intracranial arteries and intracranial aneurysms obtained at autopsy from patients without or with ADPKD.
Notably, the mitochondrial DNA copy number and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) expression were decreased in ADPKD model animal kidneys, with PGC-1α expression inversely correlated with oxidative stress levels.
An increase in the activity of the renin-angiotensin system, due to a renal ischemia caused by cyst expansion, contributes to the development of hypertension and renal failure in ADPKD.
These findings do not support the hypothesis that the enhanced ACE activity associated with the D allele might promote a significantly worse prognosis in patients with ADPKD.
This study not only provides one of the mechanisms of how c-Myc is upregulated in PKD but also suggests that targeting Brd4 with JQ1 may function as a novel epigenetic approach in ADPKD.
A role for the renin-angiotensin system (RAS) has been proposed, but studies of systemic RAS have failed to show a correlation between plasma renin activity and blood pressure in ADPKD.