Open AccessReducing YAP expression in Pkd1 mutant mice does not improve the cystic phenotype
Author(s) -
Formica Chiara,
Kunnen Sandra,
Dauwerse Johannes G.,
Mullick Adam E.,
Dijkstra Kyra L.,
Scharpfenecker Marion,
Peters Dorien J. M.
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15512
Subject(s) - hippo signaling pathway , gene knockdown , autosomal dominant polycystic kidney disease , biology , wnt signaling pathway , polycystic kidney disease , pkd1 , microbiology and biotechnology , phenotype , effector , cancer research , signal transduction , genetics , kidney , gene
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.