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@ARTICLE{Liu:288814,
author = {K. Liu and L. Wehling and S. Wan and S. M. E. Weiler and M.
Tóth and D. Ibberson and S. Marhenke and A. Ali$^*$ and M.
Lam$^*$ and T. Guo and F. Pinna and F. Pedrini and A.
Damle-Vartak and A. Dropmann and F. Rose and S. Colucci and
W. Cheng and M. Bissinger and J. Schmitt and P. Birner and
T. Poth and P. Angel$^*$ and S. Dooley and M. U.
Muckenthaler and T. Longerich and A. Vogel and M.
Heikenwälder$^*$ and P. Schirmacher and K. Breuhahn},
title = {{D}ynamic {YAP} expression in the non-parenchymal liver
cell compartment controls heterologous cell communication.},
journal = {Cellular and molecular life sciences},
volume = {81},
number = {1},
issn = {1420-682X},
address = {Cham (ZG)},
publisher = {Springer International Publishing AG},
reportid = {DKFZ-2024-00485},
pages = {115},
year = {2024},
abstract = {The Hippo pathway and its transcriptional effectors
yes-associated protein (YAP) and transcriptional coactivator
with PDZ-binding motif (TAZ) are targets for cancer therapy.
It is important to determine if the activation of one factor
compensates for the inhibition of the other. Moreover, it is
unknown if YAP/TAZ-directed perturbation affects cell-cell
communication of non-malignant liver cells.To investigate
liver-specific phenotypes caused by YAP and TAZ
inactivation, we generated mice with hepatocyte (HC) and
biliary epithelial cell (BEC)-specific deletions for both
factors (YAPKO, TAZKO and double knock-out (DKO)).
Immunohistochemistry, single-cell sequencing, and proteomics
were used to analyze liver tissues and serum.The loss of
BECs, liver fibrosis, and necrosis characterized livers from
YAPKO and DKO mice. This phenotype was weakened in DKO
tissues compared to specimens from YAPKO animals. After
depletion of YAP in HCs and BECs, YAP expression was induced
in non-parenchymal cells (NPCs) in a cholestasis-independent
manner. YAP positivity was detected in subgroups of Kupffer
cells (KCs) and endothelial cells (ECs). The secretion of
pro-inflammatory chemokines and cytokines such as C-X-C
motif chemokine ligand 11 (CXCL11), fms-related receptor
tyrosine kinase 3 ligand (FLT3L), and soluble intercellular
adhesion molecule-1 (ICAM1) was increased in the serum of
YAPKO animals. YAP activation in NPCs could contribute to
inflammation via TEA domain transcription factor
(TEAD)-dependent transcriptional regulation of secreted
factors.YAP inactivation in HCs and BECs causes liver
damage, and concomitant TAZ deletion does not enhance but
reduces this phenotype. Additionally, we present a new
mechanism by which YAP contributes to cell-cell
communication originating from NPCs.},
keywords = {Animals / Mice / Endothelial Cells / Ligands / Liver /
Hepatocytes / Cell Communication / Cholangiocyte (Other) /
Endothelial cell (Other) / Hepatocyte (Other) / Hippo
pathway (Other) / Kupffer cell (Other) / Liver damage
(Other) / Proteomics (Other) / Single-cell analysis (Other)
/ TAZ (Other) / Ligands (NLM Chemicals)},
cin = {F180 / D440 / A100},
ddc = {610},
cid = {I:(DE-He78)F180-20160331 / I:(DE-He78)D440-20160331 /
I:(DE-He78)A100-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38436764},
pmc = {pmc:PMC10912141},
doi = {10.1007/s00018-024-05126-1},
url = {https://inrepo02.dkfz.de/record/288814},
}