Cited by 412Liver physiology and pathologyHippo pathway signaling and YAP/TAZLiver Disease Diagnosis and Treatment

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The Hippo pathway effector YAP controls mouse hepatic stellate cell activation

Mannaerts, Inge, Leite, Sofia Batista, Verhulst, Stefaan, Claerhout, Sofie, Eysackers, Nathalie, Thoen, Lien F.R., Hoorens, Anne, Reynaert, Hendrik, Halder, Georg, van Grunsven, Leo A.·2015·Journal of Hepatology

DOI 10.1016/j.jhep.2015.04.011

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Abstract

Background & aims Hepatic stellate cell activation is a wound-healing response to liver injury. However, continued activation of stellate cells during chronic liver damage causes excessive matrix deposition and the formation of pathological scar tissue leading to fibrosis and ultimately cirrhosis. The importance of sustained stellate cell activation for this pathological process is well recognized, and several signalling pathways that can promote stellate cell activation have been identified, such as the TGFβ-, PDGF-, and LPS-dependent pathways. However, the mechanisms that trigger and drive the early steps in activation are not well understood. Methods and results We identified the Hippo pathway and its effector YAP as a key pathway that controls stellate cell activation. YAP is a transcriptional co-activator and we found that it drives the earliest changes in gene expression during stellate cell activation. Activation of stellate cells in vivo by CCl4 administration to mice or activation in vitro caused rapid activation of YAP as revealed by its nuclear translocation and by the induction of YAP target genes. YAP was also activated in stellate cells of human fibrotic livers as evidenced by its nuclear localization. Importantly, knockdown of YAP expression or pharmacological inhibition of YAP prevented hepatic stellate cell activation in vitro and pharmacological inhibition of YAP impeded fibrogenesis in mice. Conclusions YAP activation is a critical driver of hepatic stellat…

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Authors: Mannaerts, I., Leite, S. B., Verhulst, S., Claerhout, S., Eysackers, N., Thoen, L. F. R., Hoorens, A., Reynaert, H., Halder, G., & van Grunsven, L. A.
Affiliations: Vrije Universiteit Brussel (BE)
KU Leuven (BE)
Universitair Ziekenhuis Brussel (BE)
Corresponding author: van Grunsven, Leo A.
ORCID: Mannaerts, Inge
Leite, Sofia Batista
Verhulst, Stefaan
Claerhout, Sofie
Hoorens, Anne
Reynaert, Hendrik
Halder, Georg
van Grunsven, Leo A.
Venue: Journal of Hepatology
Publisher: Elsevier BV
Published: 2015-09
Volume: 63
Issue: 3
Pages: 679-688
ISSN: 0168-8278 (ISSN-L)
DOI: 10.1016/j.jhep.2015.04.011
OpenAlex: W2154530183
Cited by: 410
References: 46
Citations by year: 2026: 37 · 2025: 44 · 2024: 43 · 2023: 29 · 2022: 60 · 2021: 49 · 2020: 35 · 2019: 38 · 2018: 29 · 2017: 23 · 2016: 19 · 2015: 4
FWCI: 14.82
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Hepatology (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Topics: Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords: YAP, Hippo signaling pathway, hepatic stellate cell activation, liver fibrosis, YAP inhibition, carbon tetrachloride-induced liver injury, nuclear translocation, transcriptional coactivator, liver cirrhosis, fibrogenesis
MeSH terms: Hippo Signaling Pathway, YAP-Signaling Proteins, Animals, Humans, Liver Cirrhosis, Mice, Inbred BALB C, Phosphoproteins, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Adaptor Proteins, Signal Transducing, Mice, Hepatic Stellate Cells

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The Hippo pathway effector YAP controls mouse hepatic stellate cell activation

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