Thrombin and phenotypic modulation of the endothelium.
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.
Minami
Takashi
T
Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.
Sugiyama
Akira
A
Wu
Sheng-Qian
SQ
Abid
Ruhul
R
Kodama
Tatsuhiko
T
Aird
William C
WC
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
D018836:Inflammation Mediators; D018179:Receptors, Thrombin; D014157:Transcription Factors; D013917:Thrombin