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

• Published in: Journal of cellular and molecular medicine 2020-08, Vol.24 (15), p.8876-8882
• Main Authors: Formica, Chiara, Kunnen, Sandra, Dauwerse, Johannes G., Mullick, Adam E., Dijkstra, Kyra L., Scharpfenecker, Marion, Peters, Dorien J. M.
• Format: Article
• Language: English
• Subjects: 3D cysts; Adaptor Proteins, Signal Transducing - genetics; ADPKD; Animals; Antibodies; Antisense oligonucleotides; Apoptosis; ASO; Cell Line; Cysts; Disease Models, Animal; Female; Gene expression; Gene Expression Regulation; Genetic Association Studies; Genotype & phenotype; Hippo pathway; Immunohistochemistry; Kidney diseases; Kidneys; Mice; Mice, Knockout; Mutation; Myc protein; Phenotype; Phenotypes; Polycystic kidney; Polycystic Kidney Diseases - diagnosis; Polycystic Kidney Diseases - genetics; Protein Kinase C - genetics; Proteins; Short Communication; Short Communications; Signal transduction; Software; Transcription; Wnt protein; Yap/Taz; Yes-associated protein
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15512

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.