The Ion Channel, CFTR, assembles with HIPPO pathway proteins TAZ and YAP in polycystic kidney disease - PubMed
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- #CFTR
- #Polycystic Kidney Disease
- #HIPPO Pathway
- Adult-onset polycystic kidney disease (ADPKD) leads to decline in renal function, with cyst expansion critically dependent on increased proliferation.
- CFTR modulator VX-809 reduces cyst formation by creating an absorptive phenotype and inhibiting proliferation.
- CFTR closely associates with HIPPO pathway proteins TAZ and YAP, co-localizing strongly in normal and mutant (pkd1R3277C) mice.
- In mutant kidneys, CFTR, TAZ, and YAP abnormally accumulate at the apical membrane, indicative of their role in cyst growth.
- VX-809 treatment restores CFTR, TAZ, and YAP to a basolateral location similar to normal kidneys.
- CFTR, TAZ, and YAP also co-localize with ER marker calnexin, highest in untreated mutant kidneys.
- TAZ and YAP are increased in nuclei of untreated mutant kidneys compared to normal; VX-809 reduces nuclear levels to normal, providing mechanistic insight into how CFTR modulator therapy reduces proliferation.