title: Thrombin and phenotypic modulation of the endothelium.
abstract: Thrombin signaling in the endothelium is linked to multiple phenotypic changes, including alterations in permeability, vasomotor tone, and leukocyte trafficking. The thrombin signal is transduced, at least in part, at the level of gene transcription. In this review, we focus on the role of thrombin signaling and transcriptional networks in mediating downstream gene expression and endothelial phenotype. In addition, we report the results of DNA microarrays in control and thrombin-treated endothelial cells. We conclude that (1) thrombin induces the upregulation and downregulation of multiple genes in the endothelium, (2) thrombin-mediated gene expression involves a multitude of transcription factors, and (3) future breakthroughs in the field will depend on a better understanding of the spatial and temporal dynamics of these transcriptional networks.
authors.affiliation: Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Minami
authors.forename: Akira
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Sheng-Qian
authors.initials: SQ
authors.lastname: Wu
authors.forename: Ruhul
authors.initials: R
authors.lastname: Abid
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
mesh_terms: D001777:Blood Coagulation / Q000502:physiology; D042783:Endothelial Cells / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D018179:Receptors, Thrombin / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D018179:Receptors, Thrombin; D014157:Transcription Factors; D013917:Thrombin