ArticlePloS one2020
GPCR-induced YAP activation sensitizes fibroblasts to profibrotic activity of TGFβ1.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Role of YAP/TAZ Mechanobiological Signaling in Osteoporosis and Osteoarthritis.Calcified tissue international · 2026Review
- BMSCs regulate RGS3 expression in ovarian stromal cells to improve ovarian stromal fibrosis and angiogenic microenvironment in cyclophosphamide-induced premature ovarian failure.Stem cell research & therapy · 2026Article
- Dynamic Organelle Remodeling in HIV-Associated Myocardial Disease: Mechanisms, Fibrotic Pathways, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- GPCRs as key regulators in wound healing.Frontiers in cell and developmental biology · 2026Review
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Article
- PTH counteracts Hippo signaling via Src-dependent YAP stabilization to enhance bone marrow stromal cell differentiation.JCI insight · 2025Article
- Restoring Prostacyclin/PGI2-PTGIR signaling alleviates intestinal fibrosis in Crohn's disease via fibroblast-specific YAP/TAZ inhibition.Journal of Crohn's & colitis · 2025Article
- SALL4 mediates SHP2 inhibition in myocardial fibroblasts through the DOT1L/H3K79me2 signaling pathway to promote the progression of myocardial infarction.Scientific reports · 2024Article
- Gα12 and Gα13 proteins are required for transforming growth factor-β-induced myofibroblast differentiation.The Biochemical journal · 2024Article
- Review
- Critical role of Gα12 and Gα13 proteins in TGF-β-induced myofibroblast differentiation.bioRxiv : the preprint server for biology · 2024Article
- Nuclear deformation regulates YAP dynamics in cancer associated fibroblasts.Acta biomaterialia · 2024Article
- Divergent roles of the Hippo pathway in the pathogenesis of idiopathic pulmonary fibrosis: tissue homeostasis and fibrosis.Inflammation and regeneration · 2023Review
- Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury.JCI insight · 2023Article
- Dopamine Receptor D1 Is Exempt from Transforming Growth FactorThe Journal of pharmacology and experimental therapeutics · 2023Article
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- The Hippo signalling pathway and its implications in human health and diseases.Signal transduction and targeted therapy · 2022Review
- Review
- Role of Cardiac Fibroblasts in Cardiac Injury and Repair.Current cardiology reports · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue fibrosis is a pathological condition characterized by uncontrolled fibroblast activation that ultimately leads to organ failure. The TGFβ1 pathway, one of the major players in establishment of the disease phenotype, is dependent on the transcriptional co-activators YAP/TAZ. We were interested whether fibroblasts can be sensitized to TGFβ1 by activation of the GPCR/YAP/TAZ axis and whether this mechanism explains the profibrotic properties of diverse GPCR ligands. We found that LPA, S1P and thrombin cooperate in human dermal fibroblasts with TGFβ1 to induce extracellular matrix synthesis, myofibroblast marker expression and cytokine secretion. Whole genome expression profiling identified a YAP/TAZ signature behind the synergistic profibrotic effects of LPA and TGFβ1. LPA, S1P and thrombin stimulation led to activation of the Rho-YAP axis, an increase of nuclear YAP-Smad2 complexes and enhanced expression of profibrotic YAP/Smad2-target genes. More generally, dermal, cardiac and lung fibroblast responses to TGFβ1 could be enhanced by increasing YAP nuclear levels (with GPCR ligands LPA, S1P, thrombin or Rho activator) and inhibited by decreasing nuclear YAP (with Rho inhibitor, forskolin, latrunculin B or 2-deoxy-glucose). Thus, we present here a conceptually interesting finding that fibroblast responses to TGFβ1 can be predicted based on the nuclear levels of YAP and modulated by stimuli/treatments that change YAP nuclear levels. Our study contributes to better understanding of fibrosis as a complex interplay of signalling pathways and proposes YAP/TAZ as promising targets in the treatment of fibrosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.