Lysophosphatidic Acid Induces ECM Production via Activation of the Mechanosensitive YAP/TAZ Transcriptional Pathway in Trabecular Meshwork Cells.
Repository Usage Stats
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).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.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.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.
Published Version (Please cite this version)10.1167/iovs.17-23702
Publication InfoHo, Leona TY; Rao, Ponugoti; Skiba, Nikolai; & Ullmer, Christoph (2018). Lysophosphatidic Acid Induces ECM Production via Activation of the Mechanosensitive YAP/TAZ Transcriptional Pathway in Trabecular Meshwork Cells. Investigative ophthalmology & visual science, 59(5). pp. 1969-1984. 10.1167/iovs.17-23702. Retrieved from https://hdl.handle.net/10161/17216.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
More InfoShow full item record
Professor of Ophthalmology
Research in our laboratory focuses on two areas of ocular diseases- cataract and glaucoma. As it relates to lens biology, we are investigating cytoskeletal signaling pathways critical for lens development, cytoarchitecture, shape and function. Ongoing studies are focused on identification and characterization of plasma membrane cytoskeletal scaffolding proteins (e.g. Periaxin, ankyrins and dystrophin/dystroglycan) involved in regulation of lens fiber cell shape, alig
Associate Professor in Ophthalmology
My research focuses on applying mass spectrometry based proteomics to study proteins in eye tissues, cells and sub-cellular compartments to understand mechanisms of vision. An important aspect of my research is to identify proteins in different compartments of retinal photoreceptor cells, their amount and modification status at different cell states defined by the light conditions, genotype, disease etc. This information can be valuable in understanding molecular mechanisms of vision and bi
Alphabetical list of authors with Scholars@Duke profiles.