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

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.

• Authors: Chiara Formica, Sandra Kunnen, Johannes G Dauwerse, Adam E Mullick, Kyra L Dijkstra, Marion Scharpfenecker, Dorien J M Peters, DIPAK Consortium
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 15 Pg. 8876-8882 (08 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32592332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Adaptor Proteins, Signal Transducing
• YAP-Signaling Proteins
• Yap1 protein, mouse
• protein kinase D
• Protein Kinase C

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Animals
• Cell Line
• Disease Models, Animal
• Female
• Gene Expression Regulation
• Genetic Association Studies
• Immunohistochemistry
• Mice
• Mice, Knockout
• Mutation
• Phenotype
• Polycystic Kidney Diseases (diagnosis, genetics)
• Protein Kinase C (genetics)
• YAP-Signaling Proteins