Reducing YAP expression in Pkd1 mutant mice does not improve the cystic phenotype

Formica, C.; Kunnen, S.; Dauwerse, J.G.; Mullick, A.E.; Dijkstra, K.L.; Scharpfenecker, M.; Peters, D.J.M.

doi:doi:10.1111/jcmm.15512

Formica, C.; Kunnen, S.; Dauwerse, J.G.; Mullick, A.E.; Dijkstra, K.L.; Scharpfenecker, M.; Peters, D.J.M. (2020)

Reducing YAP expression in Pkd1 mutant mice does not improve the cystic phenotype

The Hippo pathway is a highly conserved signalling route involved in organ size regulation. The final effectors of this pathway are two transcriptional coactivators, yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (WWTR1 or TAZ). Previously, we showed aberrant activation of the Hippo pathway in autosomal-dominant polycystic kidney disease (ADPKD), suggesting that YAP/TAZ might play a role in disease progression. Using antisense oligonucleotides (ASOs) in a mouse model for ADPKD, we efficiently down-regulatedYaplevels in the kidneys. However, we did not see any effect on cyst formation or growth. Moreover, the expression of YAP/TAZ downstream targets was not changed, while WNT and TGF-beta pathways' downstream targetsMyc,Acta2andVimwere more expressed afterYapknockdown. Overall, our data indicate that reducing YAP levels is not a viable strategy to modulate PKD progression.