ArticleThe Journal of biological chemistry2012
P2Y2 receptor-mediated lymphotoxin-α secretion regulates intercellular cell adhesion molecule-1 expression in vascular smooth muscle cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Filamin A Regulates Cardiovascular Remodeling.International journal of molecular sciences · 2021Review
- Structural Remodeling of the Extracellular Matrix in Arteriogenesis: A Review.Frontiers in cardiovascular medicine · 2021Review
- P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction.Frontiers in pharmacology · 2020Review
- P2YOral diseases · 2018Article
- The P2YAtherosclerosis · 2017Article
- Deletion of P2Y2 receptor reveals a role for lymphotoxin-α in fatty streak formation.Vascular pharmacology · 2016Article
- Purinergic P2Y2 Receptor Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells: NEW AP-1 TRANSCRIPTION FACTOR SITE AND NEGATIVE REGULATOR.The Journal of biological chemistry · 2016Article
- Direct Evidence for P2Y2 Receptor Involvement in Vascular Response to Injury.Journal of vascular research · 2016Article
- P2Y2 nucleotide receptor mediates arteriogenesis in a murine model of hind limb ischemia.Journal of vascular surgery · 2016Article
- The P2YJournal of biomedical science and engineering · 2014Article
- The inhibitory effects of extracellular ATP on the growth of nasopharyngeal carcinoma cells via P2Y2 receptor and osteopontin.Journal of experimental & clinical cancer research : CR · 2014Article
- Role of the Lymphotoxin/LIGHT System in the Development and Maintenance of Reticular Networks and Vasculature in Lymphoid Tissues.Frontiers in immunology · 2014Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The proinflammatory cytokine lymphotoxin-α (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in vascular smooth muscle cells (VSMC) are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y(2) nucleotide receptor (P2Y(2)R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y(2)R(-/-) SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Reintroduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found that UTP-stimulated LTA secretion is not sensitive to brefeldin A, which blocks the formation of vesicles involved in protein transport from the endoplasmic reticulum to the Golgi apparatus, suggesting that P2Y(2)R/filamin-mediated secretion of LTA is independent of the endoplasmic reticulum/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y(2)R deficient in LTA secretion. These data suggest that P2Y(2)R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on vascular smooth muscle cells.
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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.