Here we describe a proof-of-concept experiment designed to explore the possibility of using gene expression-based high-throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example. The previously unrecognized ability of aurintricarboxylic acid to inhibit PDGFR signaling, discovered through a screen of 1,739 compounds, demonstrates the feasibility and generalizability of GE-HTS for the discovery of small molecule modulators of any signaling pathway of interest.
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http://dx.doi.org/10.1186/gb-2008-9-3-r47 | DOI Listing |
Nat Commun
January 2025
The Intellectual and Developmental Disabilities Research Center, The Semel Institute for Neuroscience and Human Behavior, and The Broad Stem Cell Research Center, The Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity.
View Article and Find Full Text PDFCells
December 2024
Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
Endocannabinoids have been shown to play a complex role in the pathophysiology of a number of cardiovascular disorders. In the present study, the effects of the two major endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were investigated in human coronary artery smooth muscle cells (HCASMC) and human coronary artery endothelial cells (HCAEC) with regard to potential atheroprotective and anti-inflammatory effects. In HCASMC, AEA showed an inhibitory effect on platelet-derived growth factor-induced migration, but not proliferation, independent of major cannabinoid-activatable receptors (CB, CB, TRPV1), while 2-AG left both responses unaffected.
View Article and Find Full Text PDFPLoS One
January 2025
VA Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, United States of America.
J Cell Physiol
January 2025
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Vascular regeneration plays a vital role in tissue repair yet is drastically impaired in those with a spinal cord injury (SCI). Pericytes are of great significance as they are entwined with vessel-specific endothelial cells and actively contribute to maintaining the spinal cord's vascular network. Within the neurovascular unit (NVU), subtypes of pericytes characterized by various markers such as PDGFR-β, Desmin, CD146, and NG-2 are involved in vascular regeneration in SCI repair.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Ophthalmology, Muğla Training and Research Hospital, Mugla, Turkey.
Nowadays, the use of monoclonal antibodies to target angiogenic signalling pathways is common, but, unfortunately, the clinical activity of these agents is limited. Thus, the development of approaches targeting multiple pathways for anti-angiogenic effect will lead to increase the clinical benefit. For this purpose, oleuropein, hesperidin, piperine, proanthocyanidins and retinoic acid, which have previously been proven to be bioactive components, anti-angiogenic performances were experimentally tested in retinal pigment epithelial cells.
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