ArticleInvestigative ophthalmology & visual science2018
Lysophosphatidic Acid Induces ECM Production via Activation of the Mechanosensitive YAP/TAZ Transcriptional Pathway in Trabecular Meshwork Cells.
Article in Investigative ophthalmology & visual science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low-intensity pulsed ultrasound and bone morphogenetic protein 2.Journal of cell communication and signaling · 2026Article
- Lysophosphatidic acid mediates skeletal muscle fibrosis in denervation via activation of YAP/TAZ.JCI insight · 2026Article
- Uncovering a Glaucoma-Linked Lysophosphatidic Acid-MAPK/AP-1 Fibrosis Axis in Human Trabecular Meshwork Cells and Its Modulation byInternational journal of molecular sciences · 2026Article
- Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.Cell & bioscience · 2025Article
- Lipids and lipid regulators in intraocular pressure homeostasis.Current opinion in pharmacology · 2025Review
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- SE-lncRNAs in Cancer: Classification, Subcellular Localisation, Function and Corresponding TFs.Journal of cellular and molecular medicine · 2024Review
- The role of YAP/TAZ mechanosignaling in trabecular meshwork and Schlemm's canal cell dysfunction.Vision research · 2024Review
- An Autotaxin-Induced Ocular Hypertension Mouse Model Reflecting Physiological Aqueous Biomarker.Investigative ophthalmology & visual science · 2024Article
- Targeting YAP/TAZ mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.American journal of physiology. Cell physiology · 2024Article
- Targeting YAP mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.bioRxiv : the preprint server for biology · 2023Article
- From outside to inside and back again: the lysophosphatidic acid-CCN axis in signal transduction.Journal of cell communication and signaling · 2023Article
- Simvastatin Attenuates Glucocorticoid-Induced Human Trabecular Meshwork Cell Dysfunction via YAP/TAZ Inactivation.Current eye research · 2023Article
- High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner.International journal of molecular sciences · 2023Article
- Review
- Extracellular Matrix Stiffness and TGFβ2 Regulate YAP/TAZ Activity in Human Trabecular Meshwork Cells.Frontiers in cell and developmental biology · 2022Article
- RGMa Participates in the Blood-Brain Barrier Dysfunction Through BMP/BMPR/YAP Signaling in Multiple Sclerosis.Frontiers in immunology · 2022Article
- Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions.Frontiers in cell and developmental biology · 2022Article
- Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells.International journal of molecular sciences · 2021Article
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Purpose: Lysophosphatidic acid (LPA), a bioactive lipid, has been shown to increase resistance to aqueous humor outflow (AH) through the trabecular meshwork (TM). The molecular basis for this response of the TM to LPA, however, is not completely understood. In this study, we explored the possible involvement of mechanosensitive Yes-associated protein (YAP) and its paralog, transcriptional coactivator with PDZ-binding domain (TAZ), transcriptional activation in extracellular matrix (ECM) production by LPA-induced contractile activity in human TM cells (HTM). Methods: The responsiveness of genes encoding LPA receptors (LPARs), LPA hydrolyzing lipid phosphate phosphatases (LPPs), and the LPA-generating autotaxin (ATX) to cyclic mechanical stretch in HTM cells, was evaluated by RT-quantitative (q)PCR. The effects of LPA and LPA receptor antagonists on actomyosin contractile activity, activation of YAP/TAZ, and levels of connective tissue growth factor (CTGF), and Cyr61 and ECM proteins in HTM cells were determined by immunoblotting, mass spectrometry, and immunofluorescence analyses. Results: Cyclic mechanical stretch significantly increased the expression of several types of LPARs, LPP1, and ATX in HTM cells. LPA and LPA receptor-dependent contractile activity led to increases in both, the protein levels and activation of YAP/TAZ, and increased the levels of CTGF, Cyr61, α-smooth muscle actin (α-SMA), and ECM proteins in HTM cells. Conclusions: The results of this study reveal that LPA and its receptors stimulate YAP/TAZ transcriptional activity in HTM cells by modulating cellular contractile tension, and augment expression of CTGF that in turn leads to increased production of ECM. Therefore, YAP/TAZ-induced increases in CTGF and ECM production could be an important molecular mechanism underlying LPA-induced resistance to AH outflow and ocular hypertension.
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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.