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

Reducing YAP expression in Pkd1 mutant mice does not improve the cystic phenotype. J Cell Mol Med. 2020 Jun 27;: Authors: Formica C, Kunnen S, Dauwerse JG, Mullick AE, Dijkstra KL, Scharpfenecker M, Peters DJM, DIPAK Consortium Abstract 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-regulated Yap levels 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-β pathways' downstream targets Myc, Acta2 and Vim were more expressed after Yap knockdown. Overall, our data indicate that reducing YAP levels is not a viable strategy to modulate PKD progression. PMID: 32592332 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research